Journal articles on the topic 'Genetic disorders Histopathology'
To see the other types of publications on this topic, follow the link: Genetic disorders Histopathology.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Genetic disorders Histopathology.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Alkhalifa, Shooq, Aysha Darwish, Mohamed Awadh, Salman M. Alkhalifa, and Abdulla Darwish. "Congenital Tufting Enteropathy, a Rare Cause of Diarrhea and Malnourishment in Arab Child with Genetic and Histopathology Investigations." Case Reports in Pediatrics 2023 (January 25, 2023): 1–3. http://dx.doi.org/10.1155/2023/6301065.
Full textAbstract:
Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia (IED), is a rare autosomal recessive disorder due to EPCAM gene mutation. It is a rare congenital enteropathy that presents in early infancy as an intractable diarrhea that is independent of breast formula feeding that requires life-long total parental nutrition (TPN) to acquire adequate calories and fluid intake or small bowel transplantation in severe cases. Here, we report a case of intestinal failure due to congenital tufting enteropathy in a 3-year-old girl who presented with loose stools and failure to thrive. This study aims to review the literature about CTE and discuss the clinicopathological aspects and to be able to distinguish it from other causes of congenital diarrheal disorders (CDDs).
2
Jahan, Sharmin, Muhammad Abul Hasanat, Fakhrul Alam, Mohammad Fariduddin, and Tania Tofail. "LEYDIG CELL HYPOPLASIA: A UNIQUE PARADOX IN THE DIAGNOSIS OF 46,XY DISORDERS OF SEX DEVELOPMENT." AACE Clinical Case Reports 6, no. 3 (May 2020): e117-e122. http://dx.doi.org/10.4158/accr-2019-0152.
Full textAbstract:
Objective: Disorders of sex development (DSD) are defined as conditions in which chromosomal sex is inconsistent with phenotypic sex, or in which the phenotype is not classifiable as either male or female. Mutations in genes present in X, Y or autosomal chromosomes can cause abnormalities of testis determination or 46,XY DSD. Leydig cell hypoplasia (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive endocrine syndrome of 46,XY DSD. Our objective here is to present the case of a 27-year-old, phenotypic female who presented with primary amenorrhea and later found to have LCH. Methods: We used formatted history and clinical examination followed by necessary hormonal investigations. The diagnosis was confirmed by histopathology of resected testes and genetic mutation analysis. Results: The patient's physical examination was unremarkable except 2 ovoid lumps present in the inguinovulvar region. There were no müllerian structures on sonography. Estrogen and both basal and stimulated testosterone levels were low whereas luteinizing hormone and follicle-stimulating hormone were high. Her chromosomal sex was found to be 46,XY. The histopathology of the resected inguinal lumps showed atrophic testicular change lacking Leydig cells with relative preservation of Sertoli cells. Genetic mutation analysis failed to reveal any significant aberration in the LHCGR gene. At present she is on estrogen replacement therapy having undergone bilateral orchidectomy and vaginoplasty. Conclusion: LCH represents a unique example of diagnostic dilemma in gender identification. It requires a multidisciplinary approach for optimum outcome.
3
Kammler, Gertrud, Friederike Fritzsche, Uwe Kordes, Ulrich Schüller, and Manfred Westphal. "DIPG-42. Diffuse midline gliomas, H3K27-altered as an interdisciplinary challenge." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i28. http://dx.doi.org/10.1093/neuonc/noac079.099.
Full textAbstract:
Abstract INTRODUCTION: Diffuse midline gliomas represent a particular challenge in treatment. DIPG behave like highly malignant glioma with extremely poor prognosis due to location and inoperability. Molecular genetic studies, complementary to classical histopathology, have found an entity for midline gliomas, newly described ten years ago and entered the WHO classification in 2016. This group of childhood tumor with DMG’s, H3K27-altered will be demonstrated in the following with 14 case reports from our clinic. METHODS: Clinical data of four patients with tectum/thalamic gliomas, six with diffuse intrinsic brainstem glioma, two with cerebellar, one with suprasellar, one with spinal glioma were retrospectively studied. MRI data, volume increase, contrast behavior was also analyzed. Tumor tissue was obtained by various surgical procedures and diagnostic workup included histopathology as well as genetics and epigenetics. RESULTS: 14 pediatric patients were treated from 2012 to 2021, median age 7,5 years. Leading symptoms were hydrocephalus, movement disorders, cranial nerve disorders. Four patients (29%) were partially resected, two (14%) received extended biopsy, seven (50%) were (stereo tactically) biopsied, one diagnosed by liquid biopsy (7%). Histological results revealed the presence of GBM in four cases (29 %). Subsequent methylome analyses confirmed that the tumors belonged to the group of diffuse midline gliomas, H3K27-altered. The other ten tumors (71%) were primarily assigned to this H3K27 group. CONCLUSION: The pediatric tumors of the brainstem, the further midline structures, including intraspinal manifestation show different MRI findings, histology, and clinical course. Complementary molecular genetic diagnosis is essential and a meaningful addition to the histological assignment. It is considered proven that the exclusivity of H3K27 – altered tumors of children and adolescents differs from that of IDH mutated gliomas and glioblastomas by their localization of hemispheric processes. Possible therapeutic approaches using targeted therapy require understanding of these oncological mechanisms.
4
Bolde, Saroj Ashok, Arva Ali Pirosha, Sushma N. Ramraje, and Shubhangi V. Agale. "Histopathological spectrum of disorders of sexual development: a case series of seven cases." International Journal of Research in Medical Sciences 8, no. 6 (May 26, 2020): 2303. http://dx.doi.org/10.18203/2320-6012.ijrms20202283.
Full textAbstract:
Disorders of sexual development (DSD) refer to cases in which there is a discordance among at least two of the following; genetic sex, gonadal sex, genital tract sex and phenotypic sex. DSDs are quite rare with reported incidence varying from 1 in 4,500 to 1 in 5,500. Ovotesticular disorder is amongst the rarest variety of DSD comprising only to 3-10% of all cases of DSD with only 500 cases reported till now worldwide. Frequency of MRKH syndrome is 1 in 4,500 cases and is the cause of amenorrhoea in 15% of cases of primary amenorrhoea. Authors present a case series of seven cases of DSDs with three cases diagnosed as androgen insensitivity syndrome, two cases of true ovotesticular DSD (true hermaphrodite), one case each of mixed gonadal dysgenesis and Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome. Authors received the histopathology specimen of these cases in this department which was extensively sampled to study the gonads and the other derivatives of Mullerian and Wolffian duct and to rule out presence of any malignancy.
5
Hunsaker, Michael R. "Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field." F1000Research 2 (December 27, 2013): 287. http://dx.doi.org/10.12688/f1000research.2-287.v1.
Full textAbstract:
It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on theFMR1gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to theFmr1knock-out (KO) mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).
6
Zagoriti, Zoi, Manousos E. Kambouris, George P. Patrinos, Socrates J. Tzartos, and Konstantinos Poulas. "Recent Advances in Genetic Predisposition of Myasthenia Gravis." BioMed Research International 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/404053.
Full textAbstract:
Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of autoantibodies that bind to components of the neuromuscular junction, causing the symptoms of muscular weakness and fatigability. Like most autoimmune disorders, MG is a multifactorial, noninherited disease, though with an established genetic constituent. The heterogeneity observed in MG perplexes genetic analysis even more, as it occurs in various levels, including diverse autoantigens, thymus histopathology, and age at onset. In this context of distinct subgroups, a plethora of association studies, discussed in this review, have assessed the involvement of various HLA and non-HLA related loci in MG susceptibility, over the past five years. As expected, certain HLA alleles were strongly associated with MG. Many of the non-HLA genes, such asPTPN22andCTLA-4, have been previously studied in MG and other autoimmune diseases and their association with MG has been reevaluated in more cohesive groups of patients. Moreover, novel risk or protective loci have been revealed, as in the case ofTNIP1andFOXP3. Although the majority of these results have been derived from candidate gene studies, the focal point of all recent genetic studies is the first genome-wide association study (GWAS) conducted on early-onset MG patients.
7
Werner, M., V. Kaloutsi, F. Kausche, T. Buhr, and A. Georgii. "Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders." Virchows Archiv B Cell Pathology Including Molecular Pathology 63, no. 1 (December 1993): 199–204. http://dx.doi.org/10.1007/bf02899262.
Full text
8
Lee, Wei Shern, Sarah E. M. Stephenson, Kate Pope, Greta Gillies, Wirginia Maixner, Emma Macdonald-Laurs, Duncan MacGregor, et al. "Genetic characterization identifies bottom-of-sulcus dysplasia as an mTORopathy." Neurology 95, no. 18 (August 26, 2020): e2542-e2551. http://dx.doi.org/10.1212/wnl.0000000000010670.
Full textAbstract:
ObjectiveTo determine the genetic basis of bottom-of-sulcus dysplasia (BOSD), which is a highly focal and epileptogenic cortical malformation in which the imaging, electrophysiologic, and pathologic abnormalities are maximal at the bottom of sulcus, tapering to a normal gyral crown.MethodsTargeted panel deep sequencing (>500×) was performed on paired blood and brain-derived genomic DNA from 20 operated patients with drug-resistant focal epilepsy and BOSD. Histopathology was assessed using immunohistochemistry.ResultsBrain-specific pathogenic somatic variants were found in 6 patients and heterozygous pathogenic germline variants were found in 2. Somatic variants were identified in MTOR and germline variants were identified in DEPDC5 and NPRL3. Two patients with somatic MTOR variants showed a mutation gradient, with higher mutation load at the bottom of sulcus compared to the gyral crown. Immunohistochemistry revealed an abundance of dysmorphic neurons and balloon cells in the bottom of sulcus but not in the gyral crown or adjacent gyri.ConclusionsBOSD is associated with mTOR pathway dysregulation and shares common genetic etiologies and pathogenic mechanisms with other forms of focal and hemispheric cortical dysplasia, suggesting these disorders are on a genetic continuum.
9
Henni, T., P. Gaulard, M. Divine, JP Le Couedic, D. Rocha, C. Haioun, Z. Henni, JP Marolleau, Y. Pinaudeau, and M. Goossens. "Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases." Blood 72, no. 6 (December 1, 1988): 1937–43. http://dx.doi.org/10.1182/blood.v72.6.1937.1937.
Full textAbstract:
Abstract We examined 91 specimens (from 87 patients) for the expression of B- cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3- positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.
10
Henni, T., P. Gaulard, M. Divine, JP Le Couedic, D. Rocha, C. Haioun, Z. Henni, JP Marolleau, Y. Pinaudeau, and M. Goossens. "Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases." Blood 72, no. 6 (December 1, 1988): 1937–43. http://dx.doi.org/10.1182/blood.v72.6.1937.bloodjournal7261937.
Full textAbstract:
We examined 91 specimens (from 87 patients) for the expression of B- cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3- positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.
11
Cascarino, Marine, and Stéphanie Leclerc-Mercier. "Histological Patterns of Skin Lesions in Tuberous Sclerosis Complex: A Panorama." Dermatopathology 8, no. 3 (July 4, 2021): 236–52. http://dx.doi.org/10.3390/dermatopathology8030029.
Full textAbstract:
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions.
12
Nielsen, Tue L., Tessa M. Hornsyld, Tomàs Pinós, Camilla Brolin, John Vissing, and Thomas O. Krag. "Growth Factors Do Not Improve Muscle Function in Young or Adult mdx Mice." Biomedicines 10, no. 2 (January 28, 2022): 304. http://dx.doi.org/10.3390/biomedicines10020304.
Full textAbstract:
Muscular dystrophies constitute a broad group of genetic disorders leading to muscle wasting. We have previously demonstrated that treating a muscular atrophy mouse model with growth factors resulted in increased muscle mass. In the present study, we treated the Duchenne mouse model mdx for 12 weeks with myogenic growth factors peri- and post-onset of muscular degeneration to explore the effects in the oxidative muscle soleus and the glycolytic muscle extensor digitorum longus (EDL). We found no overall beneficial effect in the peri-onset group at the conclusion of the study. In the post-onset group, the functional improvement by means of electrophysiological examinations ex vivo was mostly confined to the soleus. EDL benefitted from the treatment on a molecular level but did not improve functionally. Histopathology revealed signs of inflammation at the end of treatment. In conclusion, the growth factor cocktail failed to improve the mdx on a functional level.
13
Listyasari, Nurin Aisyiyah, Ardy Santosa, and Achmad Zulfa Juniarto. "SRY-negative in 46, XX Male Testicular DSD: a case report." Journal of Biomedicine and Translational Research 6, no. 3 (December 23, 2020): 97–100. http://dx.doi.org/10.14710/jbtr.v6i3.9088.
Full textAbstract:
Background: The sex determination process requires distinct signaling pathways to generate either testis or ovaries from the same precursor structures, the primordial gonad. Deviations of this signaling mechanism may result in disorders/differences of sex development (DSD). The 46, XX testicular DSD is a rare genetic condition identified by a discrepancy between genetic and phenotypic sex caused sex reversal syndrome. Case Presentation: We describe the case of a 5 years-old 46, XX boy with ambiguous genitalia. On physical examination he had severe hypospadias, bifid scrotum, micropenis and palpable bilateral testes. Cytogenetic analysis of patient reveals a 46, XX karyotype. Hormonal assay showed low level of FSH, LH and Testosterone and there was no evidence of Mullerian structures based on pelvic imaging. The histopathology of gonadal tissue showed a Leydig cell hyperplasia which gives the impression of Sertoli cell nodule. Polymerase chain reaction (PCR) analysis failed to identify the presence of SRY gene, therefore a diagnosis of 46, XX Testicular DSD with SRY-negative was established. Conclusion: This report presents a rare case of SRY-negative 46, XX Testicular DSD in a boy with ambiguous genitalia. A comprehensive management including clinical, cytogenetic and molecular analyses have indicated that undiscovered genetic or environmental factors needs to be elucidated. It is important to carry out further molecular testing to establish precise diagnosis of DSD and to provide appropriate genetic counseling for patients and their family.
14
Diociaiuti, Andrea, Daniele Castiglia, Marialuisa Corbeddu, Roberta Rotunno, Sabrina Rossi, Elisa Pisaneschi, Claudia Cesario, Angelo Giuseppe Condorelli, Giovanna Zambruno, and May El Hachem. "First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses." International Journal of Molecular Sciences 21, no. 20 (October 18, 2020): 7707. http://dx.doi.org/10.3390/ijms21207707.
Full textAbstract:
Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.
15
Jacinto, Joana G. P., Irene M. Häfliger, Inês M. B. Veiga, Anna Letko, Arcangelo Gentile, and Cord Drögemüller. "A frameshift insertion in FA2H causes a recessively inherited form of ichthyosis congenita in Chianina cattle." Molecular Genetics and Genomics 296, no. 6 (October 2, 2021): 1313–22. http://dx.doi.org/10.1007/s00438-021-01824-8.
Full textAbstract:
AbstractThe aim of this study was to characterize the phenotype and to identify the genetic etiology of a syndromic form of ichthyosis congenita (IC) observed in Italian Chianina cattle and to estimate the prevalence of the deleterious allele in the population. Sporadic occurrence of different forms of ichthyosis including IC have been previously reported in cattle. However, so far, no causative genetic variant has been found for bovine IC. Nine affected cattle presenting congenital xerosis, hyperkeratosis and scaling of the skin as well as urolithiasis and cystitis associated with retarded growth were examined. Skin histopathology revealed a severe, diffuse orthokeratotic hyperkeratosis with mild to moderate epidermal hyperplasia. The pedigree records indicated a monogenic recessive trait. Homozygosity mapping and whole-genome sequencing allowed the identification of a homozygous frameshift 1 bp insertion in the FA2H gene (c.9dupC; p.Ala4ArgfsTer142) located in a 1.92 Mb shared identical-by-descent region on chromosome 18 present in all cases, while the parents were heterozygous as expected for obligate carriers. These findings enable the selection against this sub-lethal allele showing an estimated frequency of ~ 7.5% in Chianina top sires. A sporadic incidence of mild clinical signs in the skin of heterozygous carriers was observed. So far, pathogenic variants affecting the encoded fatty acid 2-hydroxylase catalyzing the synthesis of 2-hydroxysphingolipids have been associated with myelin disorders. In conclusion, this study represents the first report of an FA2H-related autosomal recessive inherited skin disorder in a mammalian species and adds FA2H to the list of candidate genes for ichthyosis in humans and animals. Furthermore, this study provides a DNA-based diagnostic test that enables selection against the identified pathogenic variant in the Chianina cattle population. However, functional studies are needed to better understand the expression of FA2H in IC-affected Chianina cattle.
16
Hofmann, Inga, Daniel Kierstead, Jennie Krasker, Dean Campagna, Klaus Schmitz-Abe, Kyriacos Markianos, Michelle A. Lee, et al. "GATA2 Mutations In Pediatric Myelodysplastic Syndromes and Bone Marrow Failure." Blood 122, no. 21 (November 15, 2013): 1520. http://dx.doi.org/10.1182/blood.v122.21.1520.1520.
Full textAbstract:
Abstract Introduction Inherited bone marrow failure syndromes (IBMFS), idiopathic aplastic anemia (AA), and myelodysplastic syndromes (MDS) represent a spectrum of bone marrow failure (BMF) conditions for which the underlying genetics and pathophysiology is still poorly understood. Heterozygous germline mutations in GATA2 have recently been described in three distinct conditions that include familial MDS/AML, Emberger syndrome and MonoMac syndrome, each of which exhibits great clinical heterogeneity. The Pediatric MDS and BMF Registry was established in 2010 to carefully characterize clinical and histopathologic phenotypes and investigate the molecular basis for these disorders. To date 158 eligible patients/probands and 28 family members have been enrolled. The goal of this study was to determine the prevalence of GATA2 mutations in pediatric patients with MDS and BMF and characterize their clinical and histopathologic phenotypes. Materials and Methods Sanger sequencing of GATA2 was initially performed on 3 families with a history of familial MDS and 103 patients with sporadic appearing primary MDS, AA or an unclassified BMF enrolled in the Pediatric MDS and BMF Registry. Family members were assessed in patients with pathogenic mutation to determine if the disease was inherited or sporadic. Mutations were confirmed in somatic and germline tissue wherever possible. IBMFS were ruled out by molecular testing. Rigorous phenotype analysis included clinical and laboratory data, and standardized centralized pathology review. Whole exome sequencing (WES) was performed on a subset of patients to evaluate additional cooperating mutations and possible secondary somatic events and clonal evolution. Possible candidate genes were verified by Sanger sequencing. Results We identified pathogenic GATA2 mutations in a total of 16 individuals, including 12 patients (7 familial MDS cases and 5 sporadic MDS/BMF cases) and 4 first-degree relatives from 5 kindreds. Most mutations clustered in zinc finger 2. Previously identified mutations such as N371K and R396Q as well as novel point and frame shift mutations were identified. The median age at diagnosis was 15 years. There was strong male predominance (n=11). The clinico-pathologic diagnoses were RAEB/AML (n=4), refractory cytopenia of childhood (n=6) and MonoMac/other (n=6). Two out of the four families presented with features of Emberger syndrome. Two individuals presented with characteristic features of MonoMac Syndrome, of which one also showed bone marrow failure and pulmonary fibrosis suggestive of telomere disease. Very short telomeres (below the first percentile) were detected in all lymphocyte subsets consistent with dyskeratosis congenita (DC). However, genetic analysis did not reveal any of the known DC associated genes. Other associated pathology included severe gastrointestinal bleeding (n=2), severe polyneuropathy (n=2) and other cancers (n=1). A morphologically distinctive megakaryocytic dysplasia was a characteristic finding on histopathology. Monosomy 7 was the most common acquired cytogenetic abnormalities (n=6). Given this association we identified several additional individuals with MDS and monosomy 7 from our pathology archives and identified 2 additional patients with pathogenic GATA2 mutations. Secondary somatic mutations identified by WES included ASXL1. Thirteen out of the 14 pediatric patients with GATA2 mutations underwent hematopoietic stem cell transplant (HSCT). Ten out of these 13 patients are alive. Conclusion GATA2 mutations occur at a higher frequency than previously anticipated in pediatric MDS, and BMF, often occur sporadically and are associated with monosomy 7. While the clinical presentation is heterogeneous, the histopathologic features are often unique. Somatic genetic alterations likely play a role in clonal evolution. Given its significant implications for treatment decisions and donor selection GATA2 mutation screening should be performed on all patients with MDS, AA, and BMF disorders excluding classical IBMFS, and potential related donors. Disclosures: No relevant conflicts of interest to declare.
17
Landry, Remi L., and Monica E. Embers. "Does Dementia Have a Microbial Cause?" NeuroSci 3, no. 2 (May 17, 2022): 262–83. http://dx.doi.org/10.3390/neurosci3020019.
Full textAbstract:
The potential contribution of pathogenic microbes to dementia-inducing disease is a subject of considerable importance. Alzheimer’s disease (AD) is a neurocognitive disease that slowly destroys brain function, leading to cognitive decline and behavioral and psychiatric disorders. The histopathology of AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and abnormal aggregated tau protein in the form of neurofibrillary tangles. Observational, epidemiological, experimental, and pathological studies have generated evidence for the complexity and possible polymicrobial causality in dementia-inducing diseases. The AD pathogen hypothesis states that pathogens and microbes act as triggers, interacting with genetic factors to initiate the accumulation of Aβ, hyperphosphorylated tau protein (p-tau), and inflammation in the brain. Evidence indicates that Borrelia sp., HSV-1, VZV (HHV-2), HHV-6/7, oral pathogens, Chlamydophila pneumoniae, and Candida albicans can infect the central nervous system (CNS), evade the immune system, and consequently prevail in the AD brain. Researchers have made significant progress in understanding the multifactorial and overlapping factors that are thought to take part in the etiopathogenesis of dementia; however, the cause of AD remains unclear.
18
Jacinto, Joana G. P., Alysta D. Markey, Inês M. B. Veiga, Julia M. Paris, Monika Welle, Jonathan E. Beever, and Cord Drögemüller. "A KRT71 Loss-of-Function Variant Results in Inner Root Sheath Dysplasia and Recessive Congenital Hypotrichosis of Hereford Cattle." Genes 12, no. 7 (July 4, 2021): 1038. http://dx.doi.org/10.3390/genes12071038.
Full textAbstract:
Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).
19
Nadol Jr, Joseph B., Jan D. Marshall, and Roderick T. Bronson. "Histopathology of the Human Inner Ear in Alström's Syndrome." Audiology and Neurotology 20, no. 4 (2015): 267–72. http://dx.doi.org/10.1159/000381935.
Full textAbstract:
Alström's syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström's syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament.
20
Porras-Villamil, Julián Felipe, Ángela Catalina Hinestroza-Ruiz, Doris Juliana Parra-Sepúlveda, and Gabriela Andrea López-Moreno. "Folliculitis decalvans: a case report of satisfactory recovery after implementing isotretinoin therapy." Case reports 8, no. 1 (August 3, 2022): 9–23. http://dx.doi.org/10.15446/cr.v8n1.88800.
Full textAbstract:
Introduction: Folliculitis decalvans is a rare skin disease characterized by the presence of painful papules and pustules with an underlying neutrophilic infiltrate, usually on the scalp. Its treatment is lengthy and challenging, and recurrence is relatively common. Although its etiology is unknown, several theories explaining its development have been proposed, including colonization by Staphylococcus aureus. Case description: This is the case of a 26-year-old male healthcare worker who visited the outpatient service after experiencing a 4-year history of painful pustules on the scalp; initially these lesions were located in the occipital region, but then also started to appear in the temporal and parietal regions. After being treated for bacterial folliculitis and having several recurrences, a skin biopsy was performed, which allowed diagnosing him with folliculitis decalvans. Once the diagnosis was made, isotretinoin (20mg) treatment was implemented for a year and a half, achieving complete remission of the lesions. Conclusion: Although this case has some limitations, such as the lack of histopathology images and some control laboratory tests, it clearly shows the difficulties faced when treating this type of skin disorders and presents an overview of the use of isotretinoin, evidencing that although this drug is well tolerated, possible adverse reactions from drug interactions with trimethoprim/sulfamethoxazole may arise. In addition, this case is of great importance since the possible presence of a familial cluster of folliculitis decalvans could be confirmed, if further genetic testing is performed.
21
Jacinto, Joana G. P., Irene M. Häfliger, Eylem Emek Akyürek, Roberta Sacchetto, Cinzia Benazzi, Arcangelo Gentile, and Cord Drögemüller. "KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf." Genes 12, no. 11 (November 12, 2021): 1792. http://dx.doi.org/10.3390/genes12111792.
Full textAbstract:
Inherited channelopathies are a clinically and heritably heterogeneous group of disorders that result from ion channel dysfunction. The aim of this study was to characterize the clinicopathologic features of a Belgian Blue x Holstein crossbred calf with paradoxical myotonia congenita, craniofacial dysmorphism, and myelodysplasia, and to identify the most likely genetic etiology. The calf displayed episodes of exercise-induced generalized myotonic muscle stiffness accompanied by increase in serum potassium. It also showed slight flattening of the splanchnocranium with deviation to the right side. On gross pathology, myelodysplasia (hydrosyringomielia and segmental hypoplasia) in the lumbosacral intumescence region was noticed. Histopathology of the muscle profile revealed loss of the main shape in 5.3% of muscle fibers. Whole-genome sequencing revealed a heterozygous missense variant in KCNG1 affecting an evolutionary conserved residue (p.Trp416Cys). The mutation was predicted to be deleterious and to alter the pore helix of the ion transport domain of the transmembrane protein. The identified variant was present only in the affected calf and not seen in more than 5200 other sequenced bovine genomes. We speculate that the mutation occurred either as a parental germline mutation or post-zygotically in the developing embryo. This study implicates an important role for KCNG1 as a member of the potassium voltage-gated channel group in neurodegeneration. Providing the first possible KCNG1-related disease model, we have, therefore, identified a new potential candidate for related conditions both in animals and in humans. This study illustrates the enormous potential of phenotypically well-studied spontaneous mutants in domestic animals to provide new insights into the function of individual genes.
22
Bruder, Elisabeth, Rita Alaggio, Harry P. W. Kozakewich, Gernot Jundt, Louis P. Dehner, and Cheryl M. Coffin. "Vascular and Perivascular Lesions of Skin and Soft Tissues in Children and Adolescents." Pediatric and Developmental Pathology 15, no. 1_suppl (January 2012): 26–61. http://dx.doi.org/10.2350/11-11-1119-pb.1.
Full textAbstract:
Vascular anomalies in children and adolescents are the most common soft tissue lesions and include reactive, malformative, and neoplastic tumefactions, with a full spectrum of benign, intermediate, and malignant neoplasms. These lesions are diagnostically challenging because of morphologic complexity and recent changes in classification systems, some of which are based on clinical features and others on pathologic findings. In recent decades, there have been significant advances in clinical diagnosis, development of new therapies, and a better understanding of the genetic aspects of vascular biology and syndromes that include unusual vascular proliferations. Most vascular lesions in children and adolescents are benign, although the intermediate locally aggressive and intermediate rarely metastasizing neoplasms are important to distinguish from benign and malignant mimics. Morphologic recognition of a vasoproliferative lesion is straightforward in most instances, and conventional morphology remains the cornerstone for a specific diagnosis. However, pathologic examination is enhanced by adjunctive techniques, especially immunohistochemistry to characterize the type of vessels involved. Multifocality may cause some uncertainty regarding the assignment of “benign” or “malignant.” However, increased interest in vascular anomalies, clinical expertise, and imaging technology have contributed greatly to our understanding of these disorders to the extent that in most vascular malformations and in many tumors, a diagnosis is made clinically and biopsy is not required for diagnosis. The importance of close collaboration between the clinical team and the pathologist cannot be overemphasized. For some lesions, a diagnosis is not possible from evaluation of histopathology alone, and in a subset of these, a specific diagnosis may not be possible even after all assembled data have been reviewed. In such instances, a consensus diagnosis in conjunction with clinical colleagues guides therapy. The purpose of this review is to delineate the clinicopathologic features of vascular lesions in children and adolescents with an emphasis on their unique aspects, use of diagnostic adjuncts, and differential diagnosis.
23
Behl. "Vitamin E and Other Antioxidants in Neuroprotection." International Journal for Vitamin and Nutrition Research 69, no. 3 (May 1, 1999): 213–19. http://dx.doi.org/10.1024/0300-9831.69.3.213.
Full textAbstract:
Several pathological conditions are believed to be causally related to the generation of reactive oxygen species and free radicals including various neurodegenerative disorders. In the histopathology of Alzheimer’s disease (AD) many signs of oxidative reactions can be found building the basis of the oxidative stress hypothesis of AD. One major player in the generation of an overall oxidative microenvironment for the nerve cells is the amyloid beta protein (Abeta) of the senile plaques in brain areas affected in AD. Abeta can be neurotoxic and this toxicity is mediated by peroxides and by the peroxidation of membrane lipids leading to the lysis of the cell. Consequently, lipophilic free radical scavengers such as vitamin E and the recently discovered antioxidant activity of the female sex hormone estrogen protects neurons against the oxidative toxicity of Abeta and other AD-related oxidative insults. In a first clinical trial using vitamin E in therapy, this antioxidant could slow down the course of the disease launching further clinical investigations. Although antioxidants act as non-specific protective chemical shields for neurons and do not target specific pathological events, they are highly effective and further investigations on their activity might lead to an even more effective application of antioxidants. Since the knowledge of the pathways of neuronal cell death that occur during oxidative challenges is increasing, it will be of central interest how antioxidants can interfere with signal transduction mechanisms and therefore also modify genetic programs. As long as specific interventions are not available the optimistic data concerning the neuroprotective activity of antioxidants in vitro and in vivo underline an important role for antioxidative acting compounds for the prevention and therapy of oxidative stress-related conditions including AD.
24
Weinberg, David G., Omar M. Arnaout, Rudy J. Rahme, Salah G. Aoun, H. Hunt Batjer, and Bernard R. Bendok. "Moyamoya disease: a review of histopathology, biochemistry, and genetics." Neurosurgical Focus 30, no. 6 (June 2011): E20. http://dx.doi.org/10.3171/2011.3.focus1151.
Full textAbstract:
Object Moyamoya disease (MMD) is a rare cerebrovascular disorder involving stenosis of the major vessels of the circle of Willis and proximal portions of its principal branches. Despite concerted investigation, the pathophysiology of the disorder has not been fully elucidated. Currently, the major proteins believed to play an active role in the pathogenesis include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), transforming growth factor–β1 (TGFβ1), and granulocyte colony-stimulating factor (G-CSF). In terms of the genetics, recent literature suggests a low penetrance autosomal dominant or polygenic mode of transmission involving chromosomes 3, 6, 8, 12, and 17 for familial MMD. This review summarizes the current knowledge on the histopathology, pathophysiology and genetics of MMD. Methods A PubMed/Medline systematic study of the literature was performed, from which 45 articles regarding MMD pathophysiology were identified and analyzed. Conclusions Moyamoya disease is characterized by the intimal thickening and media attenuation of the proximal vessels of the circle of Willis as well as the development of an aberrant distal vascular network. The primary proteins that are currently implicated in the pathophysiology of MMD include VEGF, bFGF, HGF, TGFβ1, and G-CSF. Furthermore, the current literature on familial MMD has pointed to a low penetrance autosomal dominant or polygenic mode of transmittance at loci on chromosomes 3, 6, 8, 12, and 17.
25
Rech, Karen L., and Rong He. "Challenges in the Histopathologic Diagnosis of Histiocytic Neoplasms." Journal of the National Comprehensive Cancer Network 19, no. 11 (November 2021): 1305–11. http://dx.doi.org/10.6004/jnccn.2021.7098.
Full textAbstract:
Histiocytic neoplasms, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), present a diagnostic challenge due to nonspecific fibroinflammatory infiltrates and a diverse clinical presentation. The pathologist can play a key role in classification of these disorders through multidisciplinary collaboration and correlation of pathologic features with clinical and radiologic findings. The histopathologic differential diagnosis is broad, requiring knowledge of the possible diagnoses at each specific anatomic site, and a careful assessment to exclude other inflammatory and neoplastic disorders. An immunohistochemistry panel including CD163, CD1a, langerin, S100, Factor XIIIa, OCT2, and BRAF V600E can provide definitive diagnosis in LCH and RDD, whereas ECD requires classic clinical features as well as confirmation of an activating MAPK pathway mutation by genetic studies.
26
Papakonstantinou, Anastasia, Konstantinos Zacharis, Stavros Kravvaritis, Theodoros Charitos, Eleni Chrysafopoulou, and Anastasia Fouka. "Glycogen storage disease type iv: a case with histologic findings in placental tissue from first trimester miscarriage." Hellenic Journal of Obstetrics and Gynecology 18, no. 3 (July 3, 2019): 105–7. http://dx.doi.org/10.33574/hjog.1772.
Full textAbstract:
Glycogen storage disease Type IV is a rare hereditary autosomal recessive disorder caused by deficient enzymatic activity of glycogen branching enzyme (GBE) which is encoded by GBE1 gene. We hereby report the case of a 32-year-old woman presented with a first-trimester miscarriage. The histologic findings of the placental tissue included intracytoplasmic inclusion vacuoles suggested GSD‐IV. The diagnosis was confirmed by the genetic analysis of the parents, in which mother was found to be carrier of a GBE1 mutation. This variable disorder can be diagnosed by histopathology of the placenta but for its confirmation and prevention in subsequent pregnancies, genetic analysis is needed.
27
Basu, Atreyee, Surya Seshan, Luis Angel, Andre Moreira, and Fang Zhou. "A Rare Case of Hermansky-Pudlak Syndrome Involving Bilateral Lung: Histopathologic and Electron Microscopic Findings." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S42—S43. http://dx.doi.org/10.1093/ajcp/aqz113.014.
Full textAbstract:
Abstract Introduction Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive hereditary disorder characterized by oculocutaneous albinism and bleeding diathesis. Transplantation is often conducted to treat lung fibrosis, which is the most fatal complication of this disease. While the literature discusses the diagnosis of HPS based on genetic testing, radiology, and electron microscopic (EM) findings of platelet granules, there is a paucity of images in the literature illustrating the pulmonary histopathologic and EM features of HPS. Case Report Here we present striking histopathologic and EM images from a case of pulmonary fibrosis due to HPS in a 48-year-old female. The patient presented with restrictive lung disease and bilateral decreased breath sounds with diffuse crackles. She was clinically diagnosed with HPS and underwent bilateral lung transplant. On histopathology, both pneumonectomy specimens showed diffuse interstitial fibrosing and cellular pneumonitis with end-stage remodeling and type II pneumocyte (PC-II) hyperplasia. The PC-IIs had abundant foamy cytoplasm and compressed scalloped nuclei. Alveolar macrophages contained fine brown granules positive for PAS-D stain. EM analysis revealed that the PC-IIs contained numerous lamellated myelin bodies (so-called giant lamellar body degeneration) suggestive of surfactant admixed with lipid and luminal microvilli. The pigmented alveolar macrophages also contained lamellated myelin bodies, as well as clusters of single membrane-bound structures with varying size and electron density admixed with vacuolar and granular debris suggestive of ceroid deposits. Conclusion Based on light microscopy, histochemical analysis, EM, and clinical presentation, it was concluded that our findings were consistent with pulmonary changes as seen in HPS.
28
Koegel, Ashley, Venee N. Tubman, and Inga Hofmann. "Acute Lymphoblastic Leukemia in a Patient with Monomac Syndrome/GATA2 Haploinsufficiency." Blood 126, no. 23 (December 3, 2015): 3729. http://dx.doi.org/10.1182/blood.v126.23.3729.3729.
Full textAbstract:
Abstract Background: Heterozygous germline mutations in GATA2 have been described in three distinct conditions: 1) familial myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML), 2) Emberger syndrome which is characterized by lymphedema, warts and predisposition to MDS/AML, 3) MonoMac syndrome which is comprised of atypical nontuberculous mycobacterial infection, monocyte, and B and natural killer cell lymphoid deficiency. It is now recognized that these conditions represent a spectrum of hematopoietic, lymphatic and immune system disorders due to GATA2 haplosinsufficiency. MDS/AML due to GATA2 mutation shows a unique histopathology with characteristic dysplasia and is often associated with monosomy 7. Although many patients with GATA2 haploinsufficiency are initially asymptomatic the majority of patients will ultimately experience a significant complication such as severe infections due to immunodeficiency, pulmonary alveolar proteinosis (PAP), thrombotic events, bone marrow failure, MDS and progression to AML. Allogenic hematopoietic stem cell transplant (HSCT) is the only curative treatment for patients with GATA2 haploinsufficiency and those who develop MDS/AML. Here we report a unique patient who presented with with acute lymphoblastic leukemia (ALL) and was later found to have classical features of MonoMAC syndrome and GATA2 haploinsufficiency. Case Summary: A previously healthy 11 year-old girl presented with fever, cellulitis, and pancytopenia. Bone marrow biopsy and aspirate were diagnostic for B-precursor acute lymphoblastic leukemia (ALL) with associated monosomy 7 and the following karyotype: 45,XX,-7,del(9)(p13),del(10)(q24). She was treated on Dana Farber Cancer Institute (DFCI) Consortium ALL Protocol 05-001, achieving a morphological and cytogenetic remission. During induction, she developed necrotizing aspergillus pneumonia and molluscum contagiousum. Her planned course of therapy was abbreviated due to the development of restrictive lung disease associated with PAP and disseminated Mycobacterium kansasii infection. Serial off therapy bone marrow studies were obtained given poor count recovery and revealed significant morphologic dysplasia, most prominent in the megakaryocytes. These findings were reminiscent of those characteristically seen in patients with GATA2 haploinsufficiency. Her infectious complications, profound monocytopenia, PAP and bone marrow dysplasia raised concern for MonoMAC Syndrome. Sanger Sequencing of GATA2 revealed a point mutation in the regulatory enhancer region of intron 5 (c.1017+572C>T) confirming the diagnosis. More than 3 years following remission of ALL, she developed a bone marrow relapse with her initial clone. Given her diagnosis of GATA2 haploinsufficiency, HSCT was selected as consolidation therapy in second remission. She succumbed to complications of HSCT 4 months after transplantation. Conclusion: Patients with GATA2 haploinsufficiency show a heterogeneous clinical presentation and are at high risk for MDS/AML often associated with monosomy 7. The development of ALL in association with GATA2 haploinsufficiency has not been described in the literature. Hematologist and oncologists should be aware that ALL may be associated with GATA2 haploinsufficiency and should be attuned to the clinical, laboratory and histopathologic features of the MonoMAC syndrome that would prompt additional testing and potentially alter treatment regimens. As allogenic HSCT is the only definitive therapy for patients with GATA2 mutation, consideration of immediate HSCT following induction of remission should be considered in patients with ALL and GATA2 haploinsufficiency. Further, as patients with GATA2 mutations can be asymptomatic, it is imperative to screen family members for GATA2 mutations and offer genetic counselling prior to consideration as potential bone marrow donors. Disclosures No relevant conflicts of interest to declare.
29
Fatima, Rida, Areesha Batool, and Sikander Ali. "Recent Trends on Epidemiology, Histopathology, Clinical Diagnosis and Treatment Measures of Alzheimer’s Disease." Cross Current International Journal of Medical and Biosciences 1, no. 2 (April 30, 2019): 38–50. http://dx.doi.org/10.36344/ccijmb.2019.v01i02.002.
Full textAbstract:
This article describes that Alzheimer’s disease is one of the most significant neurodegenerative diseases. It is a grave public brain disorder. Many people, around the world, do not only suffer from this disease but also die due to it. This article deals with the genetic and environmental risk factors responsible for Alzheimer’s disease. Alzheimer’s disease occurs due to the deposition of misfolded amyloid proteins. Since the time when Alois Alzheimer discovered it, intensive research is being done on the clinical symptoms and possible treatments of the disease. Multiple anti amyloid β drugs had been proposed long time ago but have only limited effects. Tau based drugs have been recommended and have significant effects on the patients. Yet, many strategic therapeutic approaches are still to be explored for the complete cure of Alzheimer’s disease. Further researches and approaches had undergone various experiments to conquer this disorder
30
Sigler, Eric J., and John J. Huang. "Insight and Advancement in Hereditary Retinal Degenerations." US Ophthalmic Review 04, no. 01 (2011): 90. http://dx.doi.org/10.17925/usor.2011.04.01.90.
Full textAbstract:
Hereditary retinal degenerations comprise a diverse group of inherited genetic defects in one or more retinal or retinal pigment epithelial cellular proteins. Traditionally, anatomic classification based on clinical and histopathologic phenotype has been used to organize these disorders. In the modern era of advanced molecular biological techniques and genetic screening the current classification system may soon become obsolete, due to the fact that significant overlap between different retinal degenerations has been observed, resulting from variation in gene expression, common genetic pathways, and variable inheritance patterns. In this article, we review the various clinical disease entities, emphasize a genetic classification system, and give special attention to recent advances in molecular biology and gene therapy.
31
Alipour Tabrizi, Arash, Jafar Bordbar Azari, Reza Raoofian, Arya Hedjazi, Maliheh Dadgar Moghaddam, and Maryam Sajjadian. "A Complicated Maternal Death in the context of Genetic Disorder: A Case Report." International Journal of Medical Toxicology and Forensic Medicine 11, no. 1 (April 13, 2021): 32308.1–32308.5. http://dx.doi.org/10.32598/ijmtfm.v11i1.32308.
Full textAbstract:
Background: Investigation of the maternal cause of death and pregnancy-related death is one of the most important responsibilities of a forensic pathologist. From the public health point of view, it may help to prevent losses during and following pregnancy and save the lives of women, especially in developing countries. Methods: We report a case of maternal death with a history of neurofibromatosis type 1 who presented asymptomatic and normotensive with normal laboratory test results. Results: The first attack after delivery was associated with pulmonary edema, which led to death. Investigation during the medico-legal autopsy discovered a left suprarenal tumor with the diagnosis of pheochromocytoma, which was confirmed by further histopathology testing. Conclusion: We believe that although the association of neurofibromatosis type 1 and normotensive pheochromocytoma during pregnancy has been reported rarely, the possibility must be considered for evaluation before elective operations to adopt proper preoperative protocols.
32
Caza, Tiffany, Jared Manwaring, and Jonathan Riddell. "Recurrent, bilateral, and metastatic pheochromocytoma in a young patient with Beckwith-Wiedemann syndrome: A genetic link?" Canadian Urological Association Journal 11, no. 5 (May 9, 2017): 240. http://dx.doi.org/10.5489/cuaj.4297.
Full textAbstract:
Beckwith-Wiedemann syndrome (BWS) is a genetic disorder at chromosome 11p15 that leads to increased activity of insulin-like growth factor-2 (IGF2) and reduced activity, with no active copy of the inhibitor of cell proliferation, CDKN1C, resulting in excessive growth and increased risk of tumour formation. Isolated cases of patients with Beckwith-Wiedemann syndrome and pheochromocytoma are reported in the literature; however, none have described a molecular or cytogenetic evaluation for associated genetic abnormalities.We present a case of an adolescent female with Beckwith-Wiedemann syndrome who developed recurrent, bilateral, and metastatic pheochromocytoma despite low-risk histopathology. Genotyping studies, which evaluated for genetic predisposition to pheochromocytoma or paraganglioma (PHEO/PGL), including the PGLNext sequencing panel of 12 associated genes, and a whole genome comparative genome hybridization microarray, were performed. Genomic studies were unexpectedly negative. Additionally, the histopathology of the PHEO/PGL of our patient had low-risk features, which is unusual in cases of metastases, occurring in less than 4% of cases.1 This case suggests that the BWS in itself could predispose to formation of a PHEO/PGL phenotype with aggressive behaviour. The following manuscript summarizes the case report, reviews pertinent literature, and proposes a possible mechanism for this association.
33
Agrawal, Ashutosh, Aditi Murari, Sunil Vutukuri, and Arun Singh. "Gorlin-Goltz Syndrome: Case Report of a Rare Hereditary Disorder." Case Reports in Dentistry 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/475439.
Full textAbstract:
Introduction. Gorlin-Goltz syndrome is an inherited autosomal dominant disorder with complete penetrance and extreme variable expressivity.Case Report. The present paper highlights the importance of diagnostic criteria and histopathology in early and prompt diagnosis which will lead to proper treatment and genetic counseling of the patient.Discussion. Gorlin-Goltz syndrome is about multisystem process comprising the triad of basal cell nevi, jaw keratocysts, and skeletal anomalies. A spectrum of other neurological, ophthalmic, endocrine and genital manifestations is known to be variably associated with this triad. Diagnosis of the syndrome is based on major and minor criteria.Conclusion. This paper emphasizes the importance of oral and maxillofacial health professionals in the early diagnosis of nevoid basal cell carcinoma syndrome and in a preventive multidisciplinary approach to provide a better prognosis to the patient.
34
Hernandez, Isabel, Maria-Victoria Fernandez, Lluis Tarraga, Merce Boada, and Agustín Ruiz. "Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists." Current Alzheimer Research 15, no. 6 (April 5, 2018): 511–30. http://dx.doi.org/10.2174/1567205014666170725130819.
Full textAbstract:
Background: Frontotemporal Dementia (FTD) is a heterogeneous group of disorders and the second most frequent cause of early onset dementia making it the highest number of inherited cases. Review Summary: FTD is characterized by considerable variability in clinical, genetic and histopathologic features. Patients may present symptoms ranging from behavioural disturbances to different language disorders, with or without motor neuron disorders or associated parkinsonism. Atrophy in frontal and temporal lobes is the most relevant radiological finding. In the last 10 years, the knowledge of this clinical entity has undergone remarkable changes both genetically and histopathologically, which have served to establish more consistent clinical criteria. Until now, 10 genes causative of FTLD have been described and up to four different proteins causative of atrophy have been detected in aggregates. Conclusion: This review is mostly addressed to clinicians and aims to provide basic knowledge of these neurodegenerative disorders and clarify the complex FTD scenario.
35
Gilbert-Barness, Enid, and Lewis A. Barness. "Festschrift for Dr. John M. Opitz: Pathogenesis of cardiac conduction disorders in children genetic and histopathologic aspects." American Journal of Medical Genetics Part A 140A, no. 19 (2006): 1993–2006. http://dx.doi.org/10.1002/ajmg.a.31440.
Full text
36
Carmody, R. F., R. Khan, R. K. Shastri, B. A. Winegar, and M. F. Mafee. "Lymphoproliferative Disorders of the Orbit and Ocular Adnexa." Neurographics 10, no. 5 (October 1, 2020): 329–42. http://dx.doi.org/10.3174/ng.2000022.
Full textAbstract:
Lymphoma is the most common malignancy to affect the orbit and is frequently a diagnostic challenge for the radiologist. Any orbital and/or ocular adnexal structure may be involved with lymphoproliferative disease, and many conditions, such as idiopathic orbital inflammation and metastatic disease, may have a similar appearance on CT or MR imaging. Almost all ocular adnexal lymphomas are of the non-Hodgkin B-cell type. These vary in aggressiveness from the low-grade mucosa-associated lymphoid tissue type lymphoma to the highly malignant mantle-cell lymphoma, which is a disseminated disease with a poor prognosis. In this review article, we describe the CT and MR imaging findings in the various types of ocular adnexal lymphomas, its differential diagnosis, and prognostic implications. Histopathologic and genetic characteristics are briefly covered. Treatments of some conditions are briefly discussed.Learning Objectives: To help the reader recognize the ubiquitous imaging findings in ocular adnexal lymphoproliferative diseases and to formulate a meaningful differential diagnosis vis-a-vis conditions with similar imaging appearances.
37
Bahmad, Hisham F., Lauren Ramesar, Cecilia Nosti, Gameli Anthonio, Carole Brathwaite, Cristina Vincentelli, Amilcar A. Castellano-Sánchez, and Robert Poppiti. "Histopathologic Findings Associated with Miller–Dieker Syndrome: An Autopsy Report." Diseases 10, no. 4 (November 1, 2022): 95. http://dx.doi.org/10.3390/diseases10040095.
Full textAbstract:
Miller–Dieker syndrome (MDS) is a rare genetic disorder characterized by congenital lissencephaly (absent or diminished cerebral gyri), facial dysmorphisms, neurodevelopmental retardation, intrauterine fetal demise, and death in early infancy or childhood. We present a case of a 4-year-old girl with MDS (17p13.3p13.2 deletion) who was admitted to the hospital due to fever and increased secretions from her nose, mouth, and tracheostomy tube (as she had been on a ventilator and G-tube dependent since birth). During the course of hospitalization, she developed multiorgan failure, third spacing, and significant lactic acidosis. The patient had a cardiorespiratory arrest and expired after 4 months and 8 days of hospitalization. We provide a synopsis of the main autopsy findings, with a focus on the neuropathologic anomalies.
38
Pedrosa, Ana Luisa, Letícia Bitencourt, Rafaela Moreira Paranhos, Cristiana Afonso Leitáo, Guilherme Costa Ferreira, and Ana Cristina Simões e Silva. "Alport Syndrome: A Comprehensive Review on Genetics, Pathophysiology, Histology, Clinical and Therapeutic Perspectives." Current Medicinal Chemistry 28, no. 27 (September 8, 2021): 5602–24. http://dx.doi.org/10.2174/0929867328666210108113500.
Full textAbstract:
Background: Alport syndrome (AS) is a disease caused by mutations in COL4A3, COL4A4 or COL4A5, the genes that encode distinct chains of type IV collagen. The vast majority of cases present as an inherited disorder, although de novo mutations are present in around 10% of the cases. Methods: This non-systematic review summarizes recent evidence on AS. We discuss the genetic and pathophysiology of AS, clinical manifestations, histopathology, diagnostic protocols, conventional treatment and prognostic markers of the disease. In addition, we summarize experimental findings with novel therapeutic perspectives for AS. Results: The deficient synthesis of collagen heterotrimers throughout the organism leads to impaired basement membranes (BM) in several organs. As a result, the disease manifests in a wide range of conditions, particularly renal, ocular and auricular alterations. Moreover, leiomyomatosis and vascular abnormalities may also be present as atypical presentations. In this framework, diagnosis can be performed based on clinical evaluation, skin or renal biopsy and genetic screening, the latter being the gold standard. There are no formally approved treatments for AS, even though therapeutic options have been described to delay disease progression and increase life expectancy. Novel therapeutic targets under pre-clinical investigation included paricalcitol, sodium-glucose co-transporter- 2 inhibitors, bardoxolone methyl, anti-microRNA-21 oligonucleotides, recombinant human pentraxin-2, lysyl oxidase-like-2 blockers, hydroxypropyl-b-cyclodextrin, sodium 4-phenylbutyrate and stem cell therapy. Conclusion: AS is still a greatly under and misdiagnosed disorder. The pathophysiology is still not fully unnderstand and genetics of the disease have also some gaps. Up to know, there is no specific and effective treatment for AS. Further studies are necessary to establish novel and effective therapeutic protocols.
39
Plon, Sharon E., and Philip J. Lupo. "Genetic Predisposition to Childhood Cancer in the Genomic Era." Annual Review of Genomics and Human Genetics 20, no. 1 (August 31, 2019): 241–63. http://dx.doi.org/10.1146/annurev-genom-083118-015415.
Full textAbstract:
Developments over the past five years have significantly advanced our ability to use genome-scale analyses—including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing—to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: ( a) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, ( b) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, ( c) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and ( d) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7–10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.
40
Sharp, C. K., S. M. Bergman, J. M. Stockwin, M. L. Robbin, C. Galliani, and L. M. Guay-Woodford. "Dominantly transmitted glomerulocystic kidney disease: a distinct genetic entity." Journal of the American Society of Nephrology 8, no. 1 (January 1997): 77–84. http://dx.doi.org/10.1681/asn.v8177.
Full textAbstract:
Glomerulocystic kidney disease (GCKD) is a relatively rare condition with both a sporadic and familial occurrence. Pathologically, GCKD is characterized by cystic dilatation of Bowman's space and the initial proximal convoluted tubule. As a heritable disorder, GCKD has primarily been recognized in infants with a family history of classic, autosomal dominant polycystic kidney disease (ADPKD). Dominantly transmitted GCKD associated with either hypoplastic or normal-sized kidneys has also been reported in older children and adults. A large, three-generation African-American family with familial GCKD is characterized. Of the 20 individuals available for study, seven affected individuals were identified by renal sonogram or renal histopathology. GCKD in this family segregates as an autosomal dominant trait as evidenced by its apparent transmission from a father to his sons. A set of directed linkage strategies indicates that the distinctive GCKD phenotype in this family results from a dominantly acting mutation that disrupts a genetic locus distinct from the ADPKD loci, PKD1 and PKD2, as well the human homologue of mouse jcpk mutation, a newly described murine GCKD. These analyses are the first known genetic studies conducted in a family with heritable GCKD and post-infantile age of onset.
41
Jacinto, Joana G. P., Irene M. Häfliger, Inês M. B. Veiga, Anna Letko, Cinzia Benazzi, Marilena Bolcato, and Cord Drögemüller. "A Heterozygous Missense Variant in the COL5A2 in Holstein Cattle Resembling the Classical Ehlers–Danlos Syndrome." Animals 10, no. 11 (October 30, 2020): 2002. http://dx.doi.org/10.3390/ani10112002.
Full textAbstract:
Classical Ehlers–Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by variable degrees of skin hyperextensibility and fragility, atrophic scarring, and generalized joint hypermobility. The purpose of this study was to characterize the clinicopathological phenotype of a cEDS-affected Holstein calf and to identify the causative genetic variant associated with the disorder by whole-genome sequencing (WGS). A 3-day-old female Holstein calf was referred because of easily induced skin detachment and hyperextensibility in the neck. A complete clinical investigation was performed in the calf, dam, and maternal-grandmother. The calf and dam showed hyperextensibility of the neck skin and atrophic scarring; additionally, the calf presented skin fragility. Moreover, the histopathology of biopsies from the calf and its dam showed that the collagen bundles in affected skin areas were wavy, short, thin, and surrounded by edema and moderate to severe acute hemorrhages. Genetic analysis revealed a private heterozygous missense variant in COL5A2 (c.2366G>T; p.Gly789Val) that was present only in the calf and dam. This confirmed the diagnosis of cEDS and represents the first report of a causal variant for cEDS in cattle and the first COL5A2-related large animal model.
42
Letko, Anna, Reinie Dijkman, Ben Strugnell, Irene M. Häfliger, Julia M. Paris, Katrina Henderson, Tim Geraghty, Hannah Orr, Sandra Scholes, and Cord Drögemüller. "Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep." Genes 11, no. 10 (September 29, 2020): 1147. http://dx.doi.org/10.3390/genes11101147.
Full textAbstract:
Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940).
43
Willis, Erin, Steven A. Moore, Mary O. Cox, Vikki Stefans, Akilandeswari Aravindhan, Murat Gokden, and Aravindhan Veerapandiyan. "Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene." Child Neurology Open 9 (January 2022): 2329048X2210975. http://dx.doi.org/10.1177/2329048x221097518.
Full textAbstract:
Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein ( FKRP) gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Genetic testing identified maternal inheritance of the most common pathogenic FKRP variant c.826C>A (p.L276I). Also detected was a novel insertion and duplication on the paternally inherited FKRP allele: a single nucleotide insertion (c.948_949insC) and an eighteen nucleotide duplication (c.999_1017dup18) predicted to result in premature translation termination (p.E389*). Based on the clinical features and course of the patient, heterozygosity for the common pathogenic FKRP variant, and abnormal glycosylation of alpha-dystroglycan, we suggest that the novel FKRP insertion and duplication are pathogenic. This case expands the genetic heterogeneity of LGMDR9 and emphasize the importance of muscle biopsy for precise diagnosis.
44
Brescia, Giuseppe, Lara Alessandrini, Christian Bacci, Guido Bissolotti, Marny Fedrigo, Giacomo Contro, Samuele Frasconi, et al. "Odontogenic Chronic Rhinosinusitis: Structured Histopathology Evidence in Different Patho-Physiological Mechanisms." Biomedicines 10, no. 11 (October 31, 2022): 2768. http://dx.doi.org/10.3390/biomedicines10112768.
Full textAbstract:
An increased odontogenic chronic rhinosinusitis (oCRS) occurrence rate has quite recently been reported, likely due to an intensification of conservative dental surgery and implantology. The main aim of the study was to report for the first time the structured histopathological characteristics of the surgical specimens of oCRS. Possible associations between histopathological features and oCRS patho-physiological mechanisms were also evaluated. Structured histopathology features were investigated in the sinonasal mucosa tissue of 42 consecutive oCRS patients. Mean tissue eosinophil counts were significantly different between oCRS with radicular cysts, dental implants, or other dental diseases (p = 0.0118): mean tissue eosinophil count was higher in oCRS with dental implants. Sub-epithelial edema score and squamous metaplasia presence were significantly different when comparing the above-mentioned sub-cohorts of oCRS (p = 0.0099 and p = 0.0258). In particular, squamous metaplasia was more present in oCRS cases with radicular cysts than in those with a dental implant (p = 0.0423). Fibrosis presence was significantly different comparing the three sub-cohorts of oCRS (p = 0.0408), too. This preliminary evidence supports the hypothesis that: (i) structural histopathology can become a useful tool for clinic-pathological practice in diagnostic, therapeutic, and prognostic terms in CRS; (ii) that oCRS, as CRS in general, is a histo-pathologically heterogeneous disease; (iii) oCRS resulting from dental implants disorders can frequently be characterized as a CRS with a rich tissue eosinophilic component.
45
Natelson, Ethan A., and David Pyatt. "Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog." Advances in Hematology 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/309637.
Full textAbstract:
Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by progressive peripheral blood cytopenias associated with ineffective myelopoiesis. They are typically considered neoplasms because of frequent genetic aberrations and patient-limited survival with progression to acute myeloid leukemia (AML) or death related to the consequences of bone marrow failure including infection, hemorrhage, and iron overload. A progression to AML has always been recognized among the myeloproliferative disorders (MPD) but occurs only rarely among those with essential thrombocythemia (ET). Yet, the World Health Organization (WHO) has chosen to apply the designation myeloproliferative neoplasms (MPN), for all MPD but has not similarly recommended that all MDS become the myelodysplastic neoplasms (MDN). This apparent dichotomy may reflect the extremely diverse nature of MDS. Moreover, the term MDS is occasionally inappropriately applied to hematologic disorders associated with acquired morphologic myelodysplastic features which may rather represent potentially reversible hematological responses to immune-mediated factors, nutritional deficiency states, and disordered myelopoietic responses to various pharmaceutical, herbal, or other potentially myelotoxic compounds. We emphasize the clinical settings, and the histopathologic features, of such AMD that should trigger a search for a reversible underlying condition that may be nonneoplastic and not MDS.
46
Mullan, Erin, Mher Barbarian, Yannis Trakadis, and Brenda Moroz. "Incontinentia Pigmenti in an XY Boy: Case Report and Review of the Literature." Journal of Cutaneous Medicine and Surgery 18, no. 2 (March 2014): 119–22. http://dx.doi.org/10.2310/7750.2013.13036.
Full textAbstract:
Background: Incontinentia pigmenti (IP) is a rare genetic skin disorder with X-linked dominant inheritance and a characteristic sequence of cutaneous manifestations, which is regarded as lethal in XY males. Objective: To report a case of a surviving XY male with the common IKBKG (NEMO) gene deletion confirming IP. Methods and Results: A newborn XY male with suspected IP underwent a skin biopsy on affected tissue for histopathology. Molecular genetic testing was also performed on the specimen and revealed the common IKBKG gene deletion with a pattern suggestive of somatic mosaicism. Our findings are aligned with a PubMed literature review for XY males with IP and documented IKBKG mutation. We determined that only 10 such genetically proven cases have been reported, including our case. Conclusion: Although relatively rare, cases of IP in XY males with the common NEMO mutation have likely been underreported due to the unavailability of appropriate testing in the past. Karyotype and molecular testing should be considered when clinical suspicion of IP arises for a male patient.
47
D., Nithya Gayathri Devi, Sarawathy P., and Kopika S. "Cutaneous manifestations of systemic lupus erythematosus." International Journal of Research in Dermatology 4, no. 2 (April 25, 2018): 142. http://dx.doi.org/10.18203/issn.2455-4529.intjresdermatol20181095.
Full textAbstract:
<p class="abstract"><strong>Background:</strong> SLE is a systemic autoimmune disorder associated with polyclonal activation and interplay of genetic, environmental and hormonal events. The aim of the study was to study the incidence of mucocutaneous spectrum, precipitating factors, HPE, immunofluorescence and lab data.</p><p class="abstract"><strong>Methods:</strong> Prospective cohort study. 100 SLE patients attending MMC from August 2007 to September 2009 are included in study. Detailed history, investigations and 2 years follow up were done.<strong></strong></p><p class="abstract"><strong>Results:</strong> ACLE lesions were seen in 50% patients. Sunlight was the most common precipitating factors [55%]. Mucocutaneous lesions are seen in 45%. Fever is the most common systemic symptom in 45.45%. Photosensitivity is seen in 98% of patients. DLE lesions are seen in 83.66% of patients.98.5% of histopathology correlates with classical SLE.</p><p class="abstract"><strong>Conclusions:</strong> Most of the results correlate with previous studies with few rare observations. Incidence of SLE is less compared to the Western part of world which may be due to the genetic and environmental factors. Photosensitivity being the most common symptom and sunlight being the most common exaggerating factor in our study may be due to the unprotected environmental exposure. Age, sex, ethnic factor with genetic predisposition are the main modifying factors of the various presentation of the disorder.</p>
48
Parks, A., J. Karamchandani, Y. Troyanov, R. Massie, and EK O’Ferrall. "GP.03 Diagnostic yield of next generation sequencing and myositis autoantibody panels in patients with axial myopathy." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 46, s1 (June 2019): S6. http://dx.doi.org/10.1017/cjn.2019.79.
Full textAbstract:
Background: Axial myopathy is a rare neuromuscular disorder of variable etiology characterised by preferential involvement of the paraspinal muscles. We reviewed clinical features of patients with axial myopathies and the diagnostic yield of myositis-associated antibodies and targeted next generation sequencing panels. Methods: We performed a retrospective review of patients presenting with axial myopathy at the Montreal Neurological Hospital from 2011-2018. Data collection included clinical presentation, disease course, results of electromyography, imaging, laboratory and genetic testing, and histopathology on muscle biopsy. Results: Twenty-five patients were identified. Initial manifestation of axial weakness was head drop (15), camptocormia (8), and rigid spine (2). Autoimmune myositis was diagnosed in 9 patients, seropositive in 7 out of 7 tested for myositis-associated antibodies. Genetic testing was consistent with oculopharyngeal muscular dystrophy in one patient and RYR-1 (ryanodine receptor 1) related core myopathy in another. Local radiotherapy or spine surgery preceded the onset of axial weakness in 1 and 6 patients, respectively. Muscle biopsies were available in 17 patients and revealed myopathic changes (16), inflammatory changes (6), and myopathy with vacuoles (3). Conclusions: Recent advancements in genetic and antibody testing, combined with paraspinal muscle biopsy, allow for more precise classification and identification of potentially treatable axial myopathies.
49
Cummings, Thomas J., Leslie G. Dodd, Christopher R. Eedes, and Gordon K. Klintworth. "Hereditary Benign Intraepithelial Dyskeratosis: An Evaluation of Diagnostic Cytology." Archives of Pathology & Laboratory Medicine 132, no. 8 (August 1, 2008): 1325–28. http://dx.doi.org/10.5858/2008-132-1325-hbidae.
Full textAbstract:
Abstract Context.—Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal dominant disorder characterized by elevated epibulbar and oral plaques and hyperemic conjunctival blood vessels. The condition is predominantly seen in Native Americans belonging to the Haliwa-Saponi tribe located in northeastern North Carolina. Objective.—To determine whether HBID can be diagnosed using cytologic preparations of the conjunctiva, and whether the cytologic findings correlated with the genetic linkage involving a duplication in chromosome 4 (4q35). Design.—Cytologic preparations from conjunctival brushings in patients afflicted with HBID and from unaffected blood relatives with normal conjunctivas were compared in a masked fashion. Cytologic observations were correlated with molecular genetic analyses. Results.—Papanicolaou-stained preparations from the conjunctiva showed the typical cytologic features of HBID, including rounded squamous epithelial cells with dense homogenous orange cytoplasm and hyperchromatic, pyknotic, or crenated nuclei. All cases with the diagnostic cytologic findings of HBID had a duplication in chromosome 4 (4q35). Conclusion.—HBID is an entity with distinct clinical, histopathologic, and genetic features. The results of this study indicate the diagnosis can also be supported in an appropriate clinical setting when adequate epibulbar cytology preparations are obtained and the characteristic genetic attributes are present.
50
Mattis, Daiva M., Sa A. Wang, and Chuanyi M. Lu. "Contemporary Classification and Diagnostic Evaluation of Hypereosinophilia." American Journal of Clinical Pathology 154, no. 3 (June 11, 2020): 305–18. http://dx.doi.org/10.1093/ajcp/aqaa056.
Full textAbstract:
Abstract Objectives To provide an in-depth review of the classification and diagnostic evaluation of hypereosinophilia (HE), with a focus on eosinophilic neoplasms. Methods A review of published literature was performed, and exemplary HE cases were identified. Results Causes of HE are diverse and can be grouped under three categories: primary (neoplastic), secondary (reactive), and idiopathic. Advances in cytogenetics and molecular diagnostics have led to elucidation of the genetic basis for many neoplastic hypereosinophilic disorders. One common molecular feature is formation of a fusion gene, resulting in the expression of an aberrantly activated tyrosine kinase (TK). The World Health Organization endorsed a biologically oriented classification scheme and created a new major disease category, namely, “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2.” Rearrangement of other TK genes and activating somatic mutation(s) in TK genes have also been reported in eosinophilic neoplasms. Diagnostic evaluation of HE involves a combination of clinical, histopathologic, and immunophenotypic analyses, as well as molecular genetic testing, including next-generation sequencing-based mutation panels. The management of primary HE is largely guided by the underlying molecular genetic abnormalities. Conclusions A good knowledge of recent advances in HE is necessary to ensure prompt and accurate diagnosis, as well as to help optimize patient care.