Littérature scientifique sur le sujet « Normal Karyotype »
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Articles de revues sur le sujet "Normal Karyotype"
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Steidl, Christian, Rainer Schabla, Ulrich Germing, Barbara Hildebrandt, Thomas Noesslinger, Michael Pfeilstoecker, Aristoteles Giagounidis et al. « Sequential Cytogenetic Analyses of 577 Patients with Myelodysplastic Syndromes : Correlations between Initial Karyotype, Cytogenetic Dynamics, and Clinical Course. » Blood 106, no 11 (16 novembre 2005) : 2531. http://dx.doi.org/10.1182/blood.v106.11.2531.2531.
Texte intégralRésumé :
Abstract Myelodysplastic syndromes are dynamic diseases presenting with different clinical courses ranging from almost stable courses to rapid progression to acute myeloid leukemias. Karyotype is one of the most important prognostic factors and defines subgroups of favorable, intermediate and adverse prognosis. So far, comparably low attention has been payed on karyotypic changes occuring in sequential cytogentic examinations during the course of the disease. We retrospectively examined karyotypes of 577 patients with MDS or AML with previous history of MDS and at least two successfully performed metaphase analyses. The cytogenetic and clinical data was collected from 5 different centres of the “Kompetenznetz Akute und Chronische Leukaemien” (Duesseldorf, Duisburg, Freiburg, Goettingen, Vienna). Compared to the inital karyotype, karyotype evolution was defined as acquisition of additional aberrations, expansion of an aberrant clone by more than 20% or development of a completely aberrant karyotype after a former mosaic karyotype. According to these criteria, we found karyotype evolution in 155 cases (27%). 2–8 cytogenetic examinations have been performed per case. In 121 cases additional aberrations occured and in 34 cases the aberrant clone expanded in a subsequent analysis. In the group of patients with expansion of the aberrant clone the most frequent karyotypes were 5q- (9x) and +8 (7x). The most frequent aberrant karyotypes later acquiring additional aberrations were complex (22x) and karyotypes with two aberrations (11x), but in the vast majority of cases additional aberrations occurred on basis of a normal karyotype (70x). The most frequent additional aberrations were −7/7q- (23x), 5q- (11x) and +8 (11x). In the group of initially normal karyotypes patients with karyotype evolution had a shorter survivial (p<0.05). In summary, partial or complete momosomy 7 is the most frequent additional aberration in sequential cytogenetic analyses, indicating progression of disease. Due to their genetic instability complex karyotypes or karyotypes with 2 aberrations typically acquire additional anomalies in the course, whereas karyotypes with 5q- and +8 tend to have comparably stable courses. Furthermore, we show that also cases with a normal karyotype can harbour genetic instability as in 12% of all cases a normal karyotype evolved into an aberrant karyotype which was associated with a worse prognosis compared to stable normal karyotypes. Subgroup analyses are necessary to address correlations with therapy, time to AML progression, and the dependency on examination intervals.
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Pinar, Halit, Marshall Carpenter, Benjamin J. Martin et Umadevi Tantravahi. « Utility of Fetal Karyotype in the Evaluation of Phenotypically Abnormal Stillbirths ». Pediatric and Developmental Pathology 12, no 3 (mai 2009) : 217–21. http://dx.doi.org/10.2350/07-07-0307.1.
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The objectives of this study are to test the hypothesis that stillbirths without aneuploidy-associated phenotypes have a low incidence of karyotypic abnormalities, similar among those with and without other anatomic defects. We employed a uniform postmortem protocol to examine fetuses and placentas in 962 consecutive stillbirths measuring ≥20 weeks in clinically determined gestational age submitted to the Women and Infants Hospital Division of Perinatal Pathology from 1990 through 2005. Classification of anatomic (macroscopic) abnormalities was based on a priori criteria. Anatomic fetal abnormalities were noted in 387 cases. Conventional karyotype analysis was successfully performed on 346 fetal tissue samples, 114 in anatomically normal and 232 in anatomically abnormal fetuses. The distribution of karyotypic abnormalities among cases with and without anatomic abnormalities was compared. Of the 962 stillbirths, 40% (387) had malformations. Tissue culture for karyotype analysis was attempted in 412 cases from both groups and failed in 66 cases (16%). At the 450 to 500-band resolution level, 60 of the remaining 346 karyotypes were abnormal. Of the 232 malformation cases with successful karyotyping, 59 had phenotypic attributes indicative of aneuploidy, all of which had later karyotype confirmation. Of the remaining 173 anomalous fetuses with karyotype analysis, only 1 demonstrated a karyotypic abnormality. All 114 karyotypes performed in stillbirths without anatomic abnormalities were normal. Among ≥20-week stillbirths, aneuploid karyotypes are uncommon except in fetuses with suspect phenotypes. The 95% probability estimates of karyotype abnormality in the phenotypically abnormal and normal stillbirths, 5.5% and 5.6%, respectively, do not differ. These data do not have sufficient power to detect a small difference in rates of karyotypic abnormalities between the 2 groups of ≥20-week stillbirths. However, this series indicates that this technology is uninformative among stillborn fetuses that lack aneuploidy phenotypes.
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Göhring, Gudrun, Kathrin Thomay, Caroline Fedder, Winfried Hofmann, Hans Heinrich Kreipe et Brigitte Schlegelberger. « Telomere Shortening, TP53 Mutations and Deletions in Chronic Lymphocytic Leukemia Result in Increased Chromosomal Instability and Breakpoint Clustering in Heterochromatic Regions ». Blood 128, no 22 (2 décembre 2016) : 3220. http://dx.doi.org/10.1182/blood.v128.22.3220.3220.
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Abstract Complex karyotypes are associated with a poor prognosis in chronic lymphocytic leukemia (CLL). Using mFISH, iFISHand T/C FISH we thoroughly characterized 59 CLL patients regarding parameters known to be involved in chromosomal instability: status of the genes ATM and TP53 and telomere length (10 patients with a normal karyotype, 10 patients with an isolated deletion 11q, 19 patients with a complex karyotype without a deletion 11q and 20 patients with a complex karyotype including a deletion 11q). Among the patients with a complex karyotype, 29 of 39 (74%) showed a karyotypic evolution or a composite karyotype expressing great karyotypic heterogeneity and high chromosomal instability. Deletion of TP53 and ATM, two master regulators of DNA repair, was mutually exclusive in all but one patient. Interestingly, a deletion in 11q, either isolated or in the complex context of a complex karyotype, was associated with a significantly diminished risk (p<0.05) of carrying a mutation in TP53. In patients with loss or mutation of TP53 chromosomal breakage occurred more frequently (p<0.01) in (near-) heterochromatic regions leading to dicentric chromosomes and whole arm translocations. Telomeres of aberrant cells were significantly shorter than those of cells with a normal karyotype from the same patient. Also, median telomere length in patients with complex karyotypes was significantly shorter than of healthy controls (p<0.05) and shorter than telomere length of all other cytogenetic cohorts. Furthermore, the median telomere length of patients carrying a TP53 mutation was significantly shorter than of patients without mutation (p<0.05). We conclude that telomere shortening in combination with loss of TP53 induces increased chromosomal instability with preferential involvement of (near-) heterochromatic regions. Figure 1 a-b) Results of the Cytogenetic Data Analysis System (CyDAS) evaluation of all integratedkaryotypicdata from R-banding,iFISHandmFISHanalyses for recurrent gains and losses (a) as well as for recurrent breakpoints (b) c-f) T/C FISH on metaphases (d,e) and T/C FISHkaryograms(f,g) of patient 46 with a complex karyotype. Depicted are a normal cell (d and f) and an aberrant cell (e and f) The fluorescence intensity correlating with telomere length is higher in the normal cell than in the aberrant cell indicating telomere shortening in the aberrant cell. g)Karyogramof patient 46 aftermulticolorfluorescence in situ hybridization (mFISH) demonstrating a complex karyotype with cryptic aberrations. h) Median telomere lengths (kilobases) of normal and aberrant metaphases in three patients with CLL.*statistically significant difference (p<0.05). i) Average telomere length (kilobases) of each chromosome arm of normal and aberrant metaphases of one patient. Figure 1. a-b) Results of the Cytogenetic Data Analysis System (CyDAS) evaluation of all integratedkaryotypicdata from R-banding,iFISHandmFISHanalyses for recurrent gains and losses (a) as well as for recurrent breakpoints (b). / c-f) T/C FISH on metaphases (d,e) and T/C FISHkaryograms(f,g) of patient 46 with a complex karyotype. Depicted are a normal cell (d and f) and an aberrant cell (e and f) The fluorescence intensity correlating with telomere length is higher in the normal cell than in the aberrant cell indicating telomere shortening in the aberrant cell. / g)Karyogramof patient 46 aftermulticolorfluorescence in situ hybridization (mFISH) demonstrating a complex karyotype with cryptic aberrations. / h) Median telomere lengths (kilobases) of normal and aberrant metaphases in three patients with CLL.*statistically significant difference (p<0.05). / i) Average telomere length (kilobases) of each chromosome arm of normal and aberrant metaphases of one patient. Disclosures No relevant conflicts of interest to declare.
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Zeng, Xiangzong, Min Dai, Yu Zhang, Lingling Zhou, Ya Zhou et Qifa Liu. « Somatic Mutations Predict Poor Prognosis in Myelodysplastic Syndrome Patients with Normal Karyotypes ». Blood 136, Supplement 1 (5 novembre 2020) : 44–45. http://dx.doi.org/10.1182/blood-2020-138368.
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Purpose: Somatic mutations are common in myelodysplastic syndrome (MDS), but its risk stratification is mainly based on cytogenetics. This study was to explore the prognostic significance of somatic mutations in MDS patients with normal karyotypes. Patients and Methods: Three hundred and four patients with MDS were enrolled in this retrospective study. A genomic panel of 127 gene targets were detected by next-generation sequencing. Results: Two hundred and Eighty-one (92.4%) patients carried at least one somatic mutation, while cytogenetics identified abnormalities in 140 (46.1%) patients. The 5 most frequently mutated genes were TET2, ASXL1, EZH2, TET1, FAT1, and TET2, TP53, TET1, EP300, SF3B1 in the patients with normal karyotypes and aberrant karyotypes, respectively. When mutations detected in >5% of the whole cohort, they were included in analysis and the results showed that the frequency of TET2, TP53, ASXL1, CD101, KDM6A, SH2B3 and IL-3RA mutations was different between two groups(all P<0.05). ASXL1, CD101, KDM6A, SH2B3, IL-3RA mutations were more common in normal karyotype group, while TET2 and TP53 were more common in aberrant karyotype group. Multivariable analysis showed that age (HR 1.02; P=0.027), IPSS-R(HR 1.80; P<0.0001), TP53(HR 2.36; P<0.0001) and DNMT3A (HR 1.83, P=0.044) were the risk factors while allo-HSCT(HR 0.50; P=0.001) was a protect factor for OS in the whole cohort. For sub-group analysis, IPSS-R(HR 1.54; P=0.005; HR 1.80; P<0.0001, respectively), TP53 mutation(HR 2.49; P=0.030; HR 2.13; P=0.005, respectively) and allo-HSCT(HR 0.52; P=0.040; HR 0.37; P<0.0001, respectively) retained the prognostic significance in both the normal karyotype and aberrant karyotype group. FAT1(HR 2.32; P=0.019), DNMT3A(HR 3.32; P=0.006) and IL-7R(HR 4.35; P=0.002) mutations were unfavorable factors for OS only in the normal karyotype group. Conclusion: FAT1, IL-7R and DNMT3A mutations pretict poor prognosis in MDS patients with normal karyotypes. Key words: Somatic mutation, Next-generation sequencing, Prognosis, Myelodysplastic syndrome Disclosures No relevant conflicts of interest to declare.
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Xiao, Yajuan, Yuanlu Huang, Na Xu, Rong Lin, Xuan Zhou, Xiaozhen Xiao, Guanlun Gao et Liu Xiaoli, MD. « Chromosomal Instability : A Probable Unfavorable Prognostic Factor For Patients Of Myeloidysplastic Syndromes ». Blood 122, no 21 (15 novembre 2013) : 5243. http://dx.doi.org/10.1182/blood.v122.21.5243.5243.
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Abstract Objective Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoetic stem cell clonal disorders with a high frequency of karyotypic abnormalities (40-60%). Among karyotypic abnormalities, abnormal chromosome numbers (aneuploidy) occurs frequently. In aneuploidy, chromosomal instability (CIN) is defined as persistent mis-segregation of whole chromosomes and is caused by defects during mitosis with an odd number of chromosomes. CIN is associated with tumor heterogenesis, multidrug resistance and aggressiveness in solid tumor. Hence, we performed a one-center study on MDS patients to uncover the role of CIN in MDS clinical development. Method A total of 104 cases , 62 male and 42 female, aged from 15 years to 89 years, were tested by fluorescent in situ hybridization (FISH) and karyotypic analysis before any therapeutic intervention. According to the cytogenetic analysis of those two technology they were separated into 5 groups including: CIN, normal karyotype, complex karyotype excluding CIN, deletion chromosome 7 abnormality and other chromosomal abnormalities. All cases were followed up for a median of 19.5 months. Results Karyotyping and FISH identified 70 (67.3%) patients with abnormal karyotypes containing 32 cases of CIN, 9 cases of deletion chromosome 7 abnormality and 5 cases of complex karyotype excluding CIN. The median survival for CIN group was 13 months (incredible interval:6-20 months) compared with 23 months (incredible interval :20-27 months) in all cases, 44months in normal karyotype, 23 months in deletion chromosome 7 abnormality and 13 months in complex karyotype excluding CIN group (P=0.001 for log rank method). In CIN group, 11 cases transformed into acute leukemia with a incidence of 34% with no significant difference with total cases. And the length of time for leukemia transformation shows no significant difference between CIN group and total cases. Conclusion Chromosomal instability in MDS patients of the study revealed worst prognosis compared with other groups. This may suggest that chromosomal instability in MDS chromosomal abnormality confer a significant independent adverse impact on patients survival. However this effect might have no relation to leukemia transformation. Disclosures: No relevant conflicts of interest to declare.
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Guha, Debasree, et Sayan Banerjee. « Cyclopia syndrome with normal karyotype ». Indian Journal of Medical Research 152, no 7 (2020) : 57. http://dx.doi.org/10.4103/ijmr.ijmr_1893_19.
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Almefty, Kaith K., Svetlana Pravdenkova, Jeffrey R. Sawyer et Ossama Al-Mefty. « Impact of cytogenetic abnormalities on the management of skull base chordomas ». Journal of Neurosurgery 110, no 4 (avril 2009) : 715–24. http://dx.doi.org/10.3171/2008.9.jns08285.
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Object Cytogenetic studies of chordomas are scarce and show multiple changes involving different chromosomes. These abnormalities are implicated in the pathogenesis of chordoma, but the clinical significance of these changes is yet to be determined. In this study, the authors discuss the cytogenetic changes in a large series of skull base chordomas with long-term follow-up and focus on the impact of these changes on the prognosis, progression, and management of the disease. Methods The karyotypes of chordomas in 64 patients (36 men and 28 women) were studied in relation to survival and recurrence or progression over a mean follow-up period of 48 ± 37.5 months. The standard G-banding technique was used for karyotype analysis. Statistical analysis was performed with the Fisher exact test and ORs, and Kaplan-Meier curves were generated for survival and recurrence/progression of disease. Results Seventy-four percent of de novo chordomas had normal karyotypes and a 3% recurrence rate; there was a 45% recurrence rate in de novo tumors with abnormal karyotypes (p < 0.01). Recurrent tumors were associated with a high incidence of abnormal karyotype (75%). The OR for recurrence in lesions with an abnormal versus a normal karyotype was 12. Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. Ninety-five percent of cases with progression involved chromosome 3 and/or 13. The median survival time was 4 months when both of these chromosomes had aberrations (p = 0.02). Conclusions Chordomas with normal karyotypes were associated with a low rate of recurrence and a long patient survival, and recurrent chordomas were associated with an abnormal karyotype, disease progression, and poor survival. De novo chordomas with normal karyotypes may be amenable to radical resection and adjunctive proton beam therapy. Recurrent and de novo chordomas with abnormal karyotypes were associated with complex cytogenetic abnormalities and a poor prognosis, particularly in the presence of aberrations underlying tumor progression in chromosomes 3, 4, 12, 13, and 14.
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Hasanova A.T. et Jafarova G.A. « Relationship of human heterochromatin and congenital malformations ». Journal of Theoretical, Clinical and Experimental Morphology 2, no 3-4 (9 juin 2020) : 54–56. http://dx.doi.org/10.28942/jtcem.v2i3-4.121.
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Aim. The variability of centromeric heterochromatin of the chromosome pairs 1,9 and 16 was studied in material pro- vided by the Cytogenetic Counselling Centre.
Materials and methods. The size of bands 1q12, 9q12 and 16q11 was classified as normal, larger, very large, narrow and pericentric inversion. The karyotypes under study were divided into four groups: (I) from persons with abnormal karyotype and abnor-mal phenotype, ( I I ) from persons with abnormal phenotype and normal karyotype, (III) from healthy nearest relatives (parents and sibs) of persons with abnormal phenotype and karyotype, (I V ) from normal healthy persons with normal phenotype and karyotype without any congenital malformations in the family history.
Results. A different variability of centromeric hetero-chromatin of chromosomes 1 , 9 and 16 was observed. Quite a low variability was found in chromosome 16, while chromosomes 9 and 1 showed a high degree of variability, which was more accentuated in chromosome 9 than in chromo-some 1 .
Conclusions. In all four groups there was a similar pattern of variability with the only exception in the group of nearest relatives of children with abnormal phenotype and karyotype where an unusually narrow band 1q12 was more fre- quently detected.
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Rigolin, Gian Matteo, Francesca Cibien, Sara Martinelli, Luca Formigaro, Lara Rizzotto, Elisa Tammiso, Elena Saccenti et al. « Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with “normal” FISH : correlations with clinicobiologic parameters ». Blood 119, no 10 (8 mars 2012) : 2310–13. http://dx.doi.org/10.1182/blood-2011-11-395269.
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Abstract It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with “normal” FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features.
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McFadden, Patrick, Sarah Smithson, Robert Massaro, Jialing Huang, Gail T. Prado et Wendy Shertz. « Monozygotic Twins Discordant for Trisomy 13 ». Pediatric and Developmental Pathology 20, no 4 (24 février 2017) : 340–47. http://dx.doi.org/10.1177/1093526616686471.
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Monozygotic twins with discordant karyotypes for trisomy 13 are rare. We report a case of a spontaneously conceived pregnancy who presented with first-trimester ultrasound finding of umbilical cord cyst and increased nuchal translucency in Twin A and no abnormalities in Twin B. Amniocentesis revealed 47,XY,+13 karyotype in Twin A and 46,XY karyotype in Twin B. Selective fetal reduction was performed for Twin A. Twin B was delivered at 32 weeks gestation with normal phenotype. Peripheral blood karyotype revealed 15% mosaicism for trisomy 13 and skin fibroblast revealed 46,XY karyotype. The surviving twin will be monitored for potential complication of uniparental disomy 13 and mosaic trisomy 13. This case reinforces the need for early ultrasound and nuchal translucency measurements, especially in twin gestations.
Thèses sur le sujet "Normal Karyotype"
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Smith, S. L. L. « Elucidating molecular mechanisms of leukaemogenesis in normal karyotype AML ». Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1445120/.
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The aim of this thesis was to examine the role that gene specific mutations play in leukaemogenesis of normal karyotype (NK) acute myeloid leukaemias (AMLs), by studying the number of genes involved, types of mutations, order by which they arise and their function. AML is a stem cell disease in which the bulk of the disease is perpetuated by a rare population of leukaemic stem cells (LSCs), which arise due to an accumulation of genetic events within the target cell. Eight genes known to be mutated in AML were screened from a panel of 88 NK AML patients. One hundred and twenty-seven mutations were detected multiple mutations were common and 44% of the AMLs contained mutations that affect both differentiation and proliferation, indicating a requirement for cooperating mutations. Regions of acquired uniparental disomy (aUPD) detected by SNP arrays were found to contain homozygous mutations in genes implicated in AML, such as homozygous FLT3-ITDs on 13q, indicating that mitotic recombination can act as a second genetic event in leukaemogenesis. Semi-quantitative real-time PCR mutation specific assays, were designed against mutations in the transcription factor CEBPA. These assays were used to test AML samples which had been sorted into populations corresponding to stem cell and early progenitors in normal haematopoiesis. CEBPA mutation was detected in all compartments tested, indicating it is an early event in leukaemogenesis, which is supported by their occurrence in familial AML. Functional studies of mutations in CEBPA indicated that the 30kDa isoform of the protein was able to direct differentiation of lineage depleted cord blood mononuclear cells towards the myeloid pathway, where the addition of an ITD within the C-terminal region promoted erythroid differentiation. The work presented here demonstrates that gene specific mutations play a key role in leukaemogenesis.
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Traikov, Sofia. « Loss of heterozygosity in acute myeloid leukaemia with normal karyotype ». Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-25082.
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Loss of heterozygosity (LOH) is detectable in many forms of cancer including leukaemia. It contributes to tumorigenesis through the loss of one of the two alleles of one tumor suppressor gene at a given locus, caused by deletion or uniparental disomy (UPD). UPD can only be the result of homologous recombination. Little is known about the mechanisms of UPD and what connection this aberration has with the outcome of this disease.
In this study, 146 patients with primary AML were analysed using a novel technique based on single nucleotide polymorphisms (SNPs). Leukaemic cells and healthy T-cells from each patient were obtained using FACS-Vantage cell sorting. In cases with very few sorted cells whole genome preamplification was done. Genome-wide SNP analysis was carried out according to the standard GeneChip Mapping Assay protocol (Affymetrix, USA) using the Human Mapping 10K Arrays. Moreover, the impact of the FLT3-ITD mutation on the homologous recombination using pmHPRT-DRGFP /pCbASce vectors system and yHA2x assay was investigated.
Of 146 patients with normal karyotype LOH was found in 30 cases. The potential LOH regions, were confirmed by microsatellite analysis of short tandem repeat (STR) markers. In 21 of these cases STR-analysis of T-cells, representing the corresponding tumor-free material, confirmed the regions of partial UPD. This aberration affected different chromosomes, but most commonly chr. 2, 6, 11, 21, 13, and 7, and covered between 11.5 and 88 Mb. Interestingly, in 6 LOH cases, long stretches of homozygosity present at the same positions as in the healthy cells and in the blasts were found. The impact of this phenomenon is unknown. Additionally, chromosome losses were detected in 3 patients classified with normal karyotype according to current methods. These 9 cases were not included in the UPD positive group.
No differences were observed regarding any clinical factors including age, WBC-counts and sex. The FAB M1 subtype was observed in 47.6% of the UPD positive patients, compared to only 19.2% of the UPD negative patients (P=0.04, n=146). In addition, no correlation between FLT3-ITD, MLL-PTD and NPM1 mutations in the UPD patients was found, but the data indicate that patients with UPD have a higher rate of treatment failure.
Moreover, in this study the relationship between UPD and gene aberrations was able to be confirmed. In some cases, UPD found on chromosomes 21, 19 and 11 was correlated with mutations in the RUNX1, CEBPA and WT genes, respectively. Furthermore, AML cases with and without UPD showed different but specific gene expression profiles, revealing different expression levels for genes involved in double strand break repairs.
Furthermore, it was found that different mutations could be responsible for the increase in efficiency of HR, such as FLT3-ITD or BCR-ABL. Moreover, cells with a FLT3-ITD mutation (without wt expression) rapidly increased the HR efficiency compared with heterozygous (FLT3-ITD/wt) cells. Preliminary results showed that the high repair efficiency was mainly dependent on the translocation of RAD51.
In conclusion, SNP array technology allow the identification and mapping of LOH in AML patients with normal karyotype. The obtained data also point out the necessity of analysing tumour-free material to confirm the somatic origin of the alteration. Furthermore, the available results indicate that compared to patients without UPD, patients with UPD have a higher relapse rate, which might be used as a prognostic marker in the future. Also, it could be hypothesized that downregulation of RAD51 (for example by FLT3 inhibition) might be beneficial DNA damage occurs through the genotoxic agent by reducing the relapse risk of AML.
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Romagnoli, Simone. « Identification of Structural Variants in Acute Myeloid Leukemia with normal karyotype patients by using long-reads sequencing technology ». Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1157520.
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Acute Myeloid Leukemia (AML) accounts for approximately 25% of all leukemias in adults in the Western world, and therefore is the most frequent form of blood neoplasia. Leukemic stem cells show abnormal proliferation, activation of antiapoptotic pathways and the impairment normal cell differentiation resulting in the dysregulated production of not functional blood cells, known as blast. AML is an aggressive disease, with a relative survival rate for all ages 5 years after diagnosis of 29.5%, the clinical manifestations of AML reflect the accumulation of malignant, poorly differentiated myeloid cells within the bone marrow, peripheral blood and in other organs. Diagnostic tests are mainly constituted by blood cells count and morphology, AML diagnosis is established by the presence of >=20% myeloid blasts in the bone marrow or peripheral blood. The prognostic assessment of AML patients is of capital importance for the management of the disease and to set up risk adapted therapies. Although clinical factors play an important role in disease development, karyotype is the most independent prognostic factor to forecast patients’ survival and it is adopted to provide the framework for risk-adapted treatment approach (Deschler and Lübbert, 2006; De Kouchkovsky and Abdul-Hay, 2016). The European Leukemia Net (ELN) guidelines aims to standardize risk stratification in adult AML patients by incorporating cytogenetic and known molecular abnormalities in hot spot genes. Accordingly, AML patients could be stratified into distinct prognostic risk groups (favorable, intermediate or adverse) based on their cytogenetic and molecular profile. Although this classification is the gold standard for the stratification of patients, it is fulfilled for only the 75% of AML whereas it is poorly satisfying for those patients resulted with normal karyotype (nk) at the conventional cytogenetic analysis. Normal karyotype AML (nkAML) patients mostly belong to the intermediate risk category but they experience an extremely heterogeneous outcome that represents an unmet needs in the clinical context of AML (De Kouchkovsky and Abdul-Hay, 2016; Döhner et al., 2017). In the last few years, large-scale tumour-sequencing studies have demonstrated that the majority of cancers, including hematologic neoplasia, are driven by Structural Variants (SVs) that are, for instance, genomic rearrange- ments larger than 50 bp. SVs include insertions, translocations, inversions and Copy Number Alterations (CNAs) (deletions and duplications). The recent development of high-throughput sequencing platforms provided impressive insights into leukemia pathogenesis and contributed to consider SVs as the hallmark of the genome instability leading to the establishment of the neoplasia. Beside karyotype, SVs detection is currently addressed by Next Generation Sequencing (NGS) technologies that allow the simultaneous and accurate detection of recurrent SVs breakpoints (Schütte et al., 2019), nothwithstanding, NGS faces inaccuracy and limitations when applied to resolve wide and structurally complex SVs due to the short length (100-500 bp) of the sequencing read employed (Norris et al., 2016).
In this study, we exploited the long-reads Oxford Nanopore Sequencing technology to explore the genome of a cohort of 152 AML patient with normal cytogenetics, aiming to address the genomic analysis challenges and to identify new potential genomic biomarkers able to refine the prognostic forecasting for nkAML patients. Of 152 bone marrow samples collected at diagnosis, 85 referred to the hematology unit of the A.O.U.Careggi and 67 were prospectively collected for the AML #1310 study by the Italian Hematologic Network GIMEMA (Venditti et al., 2019).
The DNA purified from nkAML samples was used to sequence the whole genome by the nanopore long-reads approach and further analysed by the bioinformatic pipeline specifically developed for SVs calling. Two SVs caller, Sniffles (Sedlazeck et al., 2018) and cuteSV (Jiang et al., 2020), were employed for the identification of an high-confidency callset of SVs that were further clustered and filtered before correlating them with patients’ outcome data. We employed an univariate Cox proportional-hazards analysis to weight the correlation between patients’ survival and each predictor variables. Further, to better estimate the cumulative impact of multiple genome and clinical variables, we developed a multi- variate Cox regression model including those SVs selected by Cox univariate model (pvalue <.05) and other predictors such as age, white blood cells count and the known molecular abnormalities in specific hotspot genes included in the ELN guidelines (Fms related Receptor Tyrosine Kinase 3 (FLT3)-ITD, Nucleophosmin 1 (NPM1), CCAAT Enhancer Binding Protein alpha (CEBPa)). Multivariate analysis allowed to select 12 SVs, represented by genomic deletions or insertions, with high impact on patients’ leukemia free and Overall Survival (OS). Of those, 8 resulted with an HR >1 (also referred as High Risk SVs (hrSVs)), thus associated with an increased risk of death, the other with an Hazard Ratio (HR) <1 (also referred as Low-risk SVs (lrSVs)) were associated to a reduced risk of death. The following stratification of the study cohort based on the presence of hrSVs enabled the identification of a high risk group of patients (accounting for the 17% of the cohort) with an extremely poor survival (median OS time 8.27 months for the group harbouring the hrSVs compared to 62.7 month fo the other, LogRank pvalue <.0001) and a low rate of response to therapy (46% for the patients with hrSVs compared to the 80%, pvalue <.0001). Taking together, these data suggest that the employ of an emerging long-reads sequencing technology capable to detect wide SVs together with a dedicated analysis pipeline could represent a powerful tool to accurately screen the whole genome of AML patients and identify new genomic biomark- ers for the prognostic assessment of nkAML patients capable to refine the actual ELN prognostic assessment in our cohort.
inversions and Copy Number Alterations (CNAs) (deletions and duplications). The recent development of high-throughput se- quencing platforms provided impressive insights into leukemia pathogenesis and contributed to consider SVs as the hallmark of the genome instability leading to the establishment of the neo- plasia. Beside karyotype, SVs detection is currently addressed by Next Generation Sequencing (NGS) technologies that allow the simultaneous and accurate detection of recurrent SVs breakpoints (Schütte et al., 2019), nothwithstanding, NGS faces inaccuracy and limitations when applied to resolve wide and structurally com- plex SVs due to the short length (100-500 bp) of the sequencing read employed (Norris et al., 2016).
In this study, we exploited the long-reads Oxford Nanopore Se- quencing technology to explore the genome of a cohort of 152 AML patient with normal cytogenetics, aiming to address the genomic analysis challenges and to identify new potential genomic biomarkers able to refine the prognostic forecasting for nkAML patients. Of 152 bone marrow samples collected at diagnosis, 85 referred to the hematology unit of the A.O.U.Careggi and 67 were prospectively collected for the AML #1310 study by the Italian Hematologic Network GIMEMA (Venditti et al., 2019).
The DNA purified from nkAML samples was used to sequence the whole genome by the nanopore long-reads approach and further analysed by the bioinformatic pipeline specifically developed for SVs calling. Two SVs caller, Sniffles (Sedlazeck et al., 2018) and cuteSV (Jiang et al., 2020), were employed for the identification of an high-confidency call-set of SVs that were further clustered and filtered before correlating them with patients’ outcome data. We employed an univariate Cox proportional-hazards analysis to weight the correlation between patients’ survival and each predic- tor variables. Further, to better estimate the cumulative impact of multiple genome and clinical variables, we developed a multi- variate Cox regression model including those SVs selected by Cox univariate model (pvalue <.05) and other predictors such as age, white blood cells count and the known molecular abnormalities in specific hotspot genes included in the ELN guidelines (Fms related Receptor Tyrosine Kinase 3 (FLT3)-ITD, Nucleophosmin 1 (NPM1), CCAAT Enhancer Binding Protein alpha (CEBPa)). Multivariate analysis allowed to select 12 SVs, represented by genomic deletions or insertions, with high impact on patients’
leukemia free and Overall Survival (OS). Of those, 8 resulted with an HR >1 (also referred as High Risk SVs (hrSVs)), thus associ- ated with an increased risk of death, the other with an Hazard Ratio (HR) <1 (also referred as Low-risk SVs (lrSVs)) were as- sociated to a reduced risk of death. The following stratification of the study cohort based on the presence of hrSVs enabled the identification of a high risk group of patients (accounting for the 17% of the cohort) with an extremely poor survival (median OS time 8.27 months for the group harbouring the hrSVs compared to
62.7 month fo the other, LogRank pvalue <.0001) and a low rate of response to therapy (46% for the patients with hrSVs compared to the 80%, pvalue <.0001). Taking together, these data suggest that the employ of an emerging long-reads sequencing technology capable to detect wide SVs together with a dedicated analysis pipeline could represent a powerful tool to accurately screen the whole genome of AML patients and identify new genomic biomark- ers for the prognostic assessment of nkAML patients capable to refine the actual ELN prognostic assessment in our cohort.
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Grummitt, Charles Gordon. « The discovery and characterisation of the C-terminal domain of nucleophosmin : implications for Acute Myeloid Leukaemia with normal karyotype ». Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612508.
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Traikov, Sofia [Verfasser], Gerold [Akademischer Betreuer] Barth et Rolf [Akademischer Betreuer] Jessberger. « Loss of heterozygosity in acute myeloid leukaemia with normal karyotype / Sofia Traikov. Gutachter : Gerold Barth ; Rolf Jessberger. Betreuer : Gerold Barth ». Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://d-nb.info/1063279976/34.
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Borg, Isabella. « A clinical and molecular cytogenetic study of patients with mental retardation, developmental delay and dysmorphism associated with an apparently normal or balanced rearranged karyotype ». Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619597.
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Matejka, Michèle. « Etude cytogenetique du mouton (ovis aries l. ) : caryotype normal et variants chromosomiques ». Paris 7, 1987. http://www.theses.fr/1987PA077055.
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KOH, THONG CHUAN EUGENE. « Down regulation of NLK by MIR-221/222 modulates chemosensitivity to glucocorticoids in pediatric normal karyotype b-cell precursor acute lymphoblastic leukemia. La downregolazione di nemo-like kinase indotta dai MIR-221/222 modula chemiosensibilità ai glucocorticoidi nella pediatrico b-cell precursor leucemia linfattica acuta ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/30498.
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Normal karyotype pediatric B-cell precursor ALL patients are heterogeneous with respect to chemotherapy response, relapse rates and prognosis and the reason is unknown. These patients are treated with a standard protocol, and stratified using MRD methodology that shows they have variable responses and predicted outcomes. This study aims to determine the reasons behind such heterogeneity. This study shows that through miRNA profiling, miR-221/222 are differentially expressed in normal karyotype patients and are up regulated in Poor Responder patients. Through proliferation, apoptosis, viability assays and cell cycle analysis, proliferation advantage was identified as the main cause of resistance to glucocorticoid treatment in miR-221/222 over expressing cell lines. SMAD1 and CREBBP were down regulated in miR-221/222 over expressing cell lines implicating the dysregulation of TGFβ and glucocorticoid-receptor pathways, while NLK was identified as a novel target of miR-221/222 through which resistance to chemotherapy is mediated.
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Király, Franz. « Vergleich verschiedener Postremissionsstrategien bei der akuten myeloischen Leukämie mit normalem Karyotyp ». [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-64963.
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Stirner, Christoph [Verfasser]. « Evaluation prognostischer Genexpressionsprofile bei der AML mit normalem Karyotyp / Christoph Stirner ». Ulm : Universität Ulm. Medizinische Fakultät, 2011. http://d-nb.info/1018024670/34.
Texte intégralLivres sur le sujet "Normal Karyotype"
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Archer, Nick, et Nicky Manning. Nuchal translucency and the heart. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199230709.003.0019.
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Introduction 264The nuchal scan 266Management 268Nuchal translucency describes sonolucent tissue in the posterior aspect of the fetal neck; the size can be measured with accuracy during the 1st trimester of pregnancy and an increase in the measurement is associated with an increased risk of chromosomal abnormality. If fetal karyotype is normal: ...
Chapitres de livres sur le sujet "Normal Karyotype"
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Velagaleti, Gopalrao V. N., et Vijay S. Tonk. « Methods of Studying Human Chromosomes and Nomenclature. The Normal Human Karyotype ». Dans Atlas of Human Chromosome Heteromorphisms, 11–31. Dordrecht : Springer Netherlands, 2004. http://dx.doi.org/10.1007/978-94-017-0433-5_2.
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Lemež, P., J. Gáliková et T. Haas. « Are there Two Main Categories of de Novo Acute Myeloid Leukemias with a Normal Karyotype ? » Dans Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, 54–60. Berlin, Heidelberg : Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-18156-6_10.
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Tariverdian, Gholamali. « Normaler weiblicher Karyotyp : 46, XX ». Dans Bildtafeln für die genetische Beratung, 9. Berlin, Heidelberg : Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-76495-0_5.
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Tariverdian, Gholamali. « Normaler männlicher Karyotyp : 46, XY ». Dans Bildtafeln für die genetische Beratung, 11. Berlin, Heidelberg : Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-76495-0_6.
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Chudoba, I., S. Metzkel, K. Blumenstengel, H. J. Fricke, K. Junker, C. Bleck, K. Hoffken et U. Claussen. « FISH Analysis in Acute Leukemia with Initially Abnormal Karyotypes and Normal Karyotypes in Relapse ». Dans Acute Leukemias VI, 54–59. Berlin, Heidelberg : Springer Berlin Heidelberg, 1997. http://dx.doi.org/10.1007/978-3-642-60377-8_10.
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Rushton, D. I. « The Nature and Causes of Spontaneous Abortions with Normal Karyotypes ». Dans Issues and Reviews in Teratology, 21–63. Boston, MA : Springer US, 1985. http://dx.doi.org/10.1007/978-1-4613-2495-9_2.
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Hasserjian, R. P. « Normal-Karyotype Acute Myeloid Leukemia ». Dans Pathobiology of Human Disease, 1644–63. Elsevier, 2014. http://dx.doi.org/10.1016/b978-0-12-386456-7.04103-4.
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Meschede, Dieter, et Eberhard Nieschlag. « Klinefelter’s syndrome ». Dans Oxford Textbook of Endocrinology and Diabetes, 1398–402. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.9076.
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When in 1942 Harry Klinefelter and his colleagues described the condition carrying his name (1), its aetiology was unknown. In 1959 Jacobs and Strong (2) recognized the chromosomal basis of the disorder, until then solely defined through a set of clinical criteria. Ever since, diagnosing Klinefelter’s syndrome has required the demonstration of the 47,XXY karyotype or one of its rare variants. The occasional patient with a normal karyotype who fulfils the original clinical criteria, namely small testes, azoospermia, gynaecomastia, and elevated urinary FSH, is no longer considered as having Klinefelter’s syndrome (3). Individuals with the karyotypes 48,XXYY, 48,XXXY, and 49,XXXXY are also subsumed under the Klinefelter’s syndrome category. While these patients display all the signs and symptoms typical of the 47,XXY karyotype, they are burdened by significant additional health problems, most notably mental retardation, and malformations. For this reason, these conditions should be designated as 48,XXYY, 48,XXXY, or 49,XXXXY syndromes, respectively, and should be set apart from Klinefelter’s syndrome in the narrower sense.
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Meschede, Dieter, et Eberhard Nieschlag. « XYY male ». Dans Oxford Textbook of Endocrinology and Diabetes, 1403–4. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.9082.
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Men with a 47,XYY karyotype do not present with a well-defined clinical syndrome. The diagnosis relies entirely on the cytogenetic demonstration of two Y chromosomes, accompanying an otherwise normal set of chromosomes. Cases with 47,XYY/46,XY mosaicism are also subsumed under the XYY male category. The 48,XXYY karyotype is briefly discussed in Chapter 9.4.3.
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Ahmed, S. Faisal, et Angela K. Lucas-Herald. « Normal and abnormal sexual differentiation ». Dans Oxford Textbook of Medicine, sous la direction de Mark Gurnell, 2435–48. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0257.
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Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype). The constitutive sex in fetal development is female. Disorders of sex development (DSD) can be classified into three broad categories based on the knowledge of the karyotype: sex chromosome abnormality (e.g. X/XY, mixed gonadal dysgenesis); XX DSD (e.g. congenital adrenal hyperplasia); XY DSD (e.g. partial androgen insensitivity syndrome).
Actes de conférences sur le sujet "Normal Karyotype"
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Fyrberg, Anna, Kourosh Lofti, Esbjorn Paul, Christer Paul, Hareth Nahi et Henrik Gréen. « Abstract 2757 : NT5C2 single nucleotide polymorphisms affects survival and response inde novoAML patients with normal karyotype ». Dans Proceedings : AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010 ; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2757.
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Silva, Bruno Custódio, Guilherme Parmigiani Bobsin, Raquel dos Santos Ramos, Tatiane Andressa Gasparetto, Vivianne Amanda do Nascimento, Paulo Ricardo Gazzola Zen et Rafael Fabiano Machado Rosa. « Clinical and neurological findings of a patient with a complex chromosome 5 alteration ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.080.
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Context: Inversion-duplication-deletion (invdupdel) involving the short arm of chromosome 5 is considered a complex and extremely rare alteration. Case report: A female patient was born prematurely at 32 weeks and was delivered by cesarean section, weighing 2,086 grams, with an Apgar score in the fifth minute of 7. After birth, she needed invasive mechanical ventilation. A nasofibrolaryngoscopy was performed, which revealed the rear projection of the tongue base. The speech-language evaluation showed a swallowing disorder. The patient needed to be tracheostomized and evolved with episodes of cardiorespiratory arrest. A zone 2 of immaturity was identified in both eyes. Then, gastroesophageal reflux was also diagnosed. Cerebral ultrasound showed moderate lateral ventricles dilation. High resolution GTG-banding karyotype identified an inverted and partial duplication of the chromosome’s 5 short arm, with a probable deletion of its distal segment: 46,XX,invdup(5) (p13.3->p15.33:: p15.33->qter) [23]. The parents’ karyotype was normal. At 2 months, the patient had dolichocephaly; bitemporal narrowing; hypertelorism; and down slanting palpebral fissures with blepharophimosis; low-set and posteriorly rotated ears; leftover skin at neck and bilateral plantar creases between the first, second and third toes. Conclusions: Invdupdel of the short arm of chromosome 5 is a very rare chromosomal alteration. Neurological findings seem to be part of its clinical manifestations, especially dilated lateral ventricles. More reports will be essential for understanding its clinical spectrum.
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Jakobsen Falk, Ingrid, Anna Fyrberg, Monica Hermanson, Martin Höglund, Hareth Nahi, Lars Palmqvist, Christer Paul et al. « Abstract 1170 : Correlation between cytidine deaminase single nucleotide polymorphisms andin vitrodrug sensitivity, DNA methylation and outcome in normal karyotype acute myelogenous leukemia. » Dans Proceedings : AACR 104th Annual Meeting 2013 ; Apr 6-10, 2013 ; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1170.
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Youk, Jeonghwan, Sunghoon Cho, Daeyoon Kim, Youngil Koh, Inho Kim, Murim Choi et Sung-Soo Yoon. « Abstract 5225 : CDK11B, PTPRN2 and WDPCP were frequently duplicated genes in refractory/relapsed normal karyotype AML patients : Identifying structural variations using whole genome sequencing ». Dans Proceedings : AACR 107th Annual Meeting 2016 ; April 16-20, 2016 ; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-5225.
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Silva, Bruno Custódio, Thais Vanessa Salvador, Jéssica Karine Hartmann, Laira Francielle Ferreira Zottis, Mateus Arenhardt de Souza, Paulo Ricardo Gazzola Zen et Rafael Fabiano Machado Rosa. « Neurological findings in a patient with mosaic chromosome 8 trisomy ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.071.
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Context: Mosaic chromosome 8 trisomy is a rare genetic disease that can develop with neurological abnormalities. Case report: A male patient had a deficit in weight gain since his first month of life, in addition to delayed speech and neuropsychomotor. At 2 years old, the family noticed that he did not see well, and then began an ophthalmological investigation that resulted in the diagnosis of bilateral congenital cataract. Moreover, it was observed that the child had microcephaly, epicanthus, and strabismus converging to the right. Abdominal ultrasound showed hepatosplenomegaly and asymmetric kidneys. Computed tomography scan of the skull was normal. Chest radiography showed an increase in cardiac volume. Bone scintigraphy revealed heterogeneous uptake of the tracer radius in the projection of the femoral diaphyses, in addition to bilateral distal femoral hypertension, with central hypoactivity being more evident on the left. Blood karyotype exhibited a mosaic chromosome 8 trisomy (mos 47, XY, + 8 [10] / 46, XY [12]). His first medullogram had been normal; however, the new test showed myelodysplasia. Conclusions: Mosaic chromosome 8 trisomy is a chromosomal abnormality characterized by quite varied clinical manifestations. Neurological changes may be present, among which are seizures. There is also a description of agenesis of the corpus callosum. In our case, speech and neuropsychomotor delay was noteworthy.
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Silva, Bruno Custódio, Tainá Alano, Lennon Vidori, Paulo Ricardo Gazzola Zen et Rafael Fabiano Machado Rosa. « Multiple contractures and their relationship with congenital amyoplasia ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.070.
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Context: Congenital amyoplasia is characterized by contractures (arthrogryposis) involving multiple large joints. Case report: The patient is a couple’s first daughter and no history of similar cases in the family. She was born at term, by cesarean delivery, weighing 3080 grams and with Apgar scores of 8 and 9. Gestational ultrasound revealed fetal akinesia, oligodramnia, and altered fetal skeletal musculature with shortening of the four limbs. During delivery, she suffered a fracture of the right femur. The patient evolved with a delay in neuropsychomotor development. On physical examination, hypotonia, nevus flammeus on the forehead, contractures involving several joints (including fingers, elbows, hips, knees and feet) were observed as well as pits in elbows and knees. Computed tomography scan of the skull showed cortical hypoplasia. Radiographic evaluation showed levoconvex thoracolumbar scoliosis and congenital changes in vertebral bodies of the thoracic spine, and thinning bone structures of the upper limbs. In addition, there were dysplastic acetabular, signs of constriction or tissue band in distal third of the right and middle thighs of the left, intense muscular hypotrophy, thinning of diaphysis of the femurs and echinovirus feet. Abdominal ultrasound and karyotype were normal. Conclusions: The clinical findings were compatible with those of congenital amyoplasia. Fetal akinesia or hypokinesia is a finding widely reported by mothers of children with this condition, as occurred in our case. Therefore, early interventions are very important, in order to avoid, in particular, greatest atrophy of the affected limbs, in addition to osteopenia.
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Silva, Bruno Custódio, Maria Isabelle Nakano Vieira, Gisele Delazeri, Esther Rodrigues Rocha Alves, Ana Luíza Kolling Konopka, Guilherme Rocha Spiller, Paulo Ricardo Gazzola Zen et Rafael Fabiano Machado Rosa. « Neurological findings of a patient with Patau syndrome and a nonusual clinical presentation ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.073.
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Context: Chromosome 13 trisomy, or Patau syndrome (PS), is a genetic condition characterized by multiple findings and usually poor survival rate. However, its clinical presentation can be variable. Case report: A male patient was referred for evaluation due to a syndromic aspect. He was born by normal delivery, at term, weighing 4700 g. On physical exam, at 2 months, two areas of scaly aplasia on the scalp were shown as well as left coloboma of the iris, bulbous nose with small nostrils, ears with oversized helices, micrognathia, umbilical hernia, clinodactyly of the index finger of the hand left and the 4th and 5th toes of the left foot. Echocardiography revealed tetralogy of Fallot. The karyotype showed a free trisomy of chromosome 13 (47, XY, + 13), compatible with the diagnosis of PS. The patient died at 9 months of age due to complications from bronchopneumonia and had evolved with a delay in neuropsychomotor development at that moment. Conclusions: There are findings that stand out among patients with PS and that very often lead to diagnosis, such as micro/anophthalmia, bilateral cleft lip/palate and polydactyly. It is interesting in our case that the patient did not have any of them, which made it difficult to identify. In addition, from a neurological point of view, the findings were quite common; however, in our patient, there was only a delay in neuropsychomotor development, pointing out that the neurological findings can also be quite variable.
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Oliveira, Jefferson Borges de, Caroline Berthier Zanin, Gustavo Carreira Henriques, Maiévi Liston, Rafael Glória Zatta, Rodrigo de Faria Martins et Tatiana Pizzolotto Bruch. « Pallister-Hall Syndrome - case report ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.575.
Texte intégralRésumé :
In 1980, Hall et all described a syndrome characterized by “hamartoblastoma”, hypopituitarism, unperfurated anus, polydactyly postaxial and numerous visceral anomalies, today known as Pallister-Hall Syndrome. On the study, Hall et all reported six cases of children with that malformation syndrome - lethal on neonatal period. None of the newborns had anterior hypophysis and the hypothalamic tumor was apparent in the inferior part of the brain, going from the optic chiasm to the interpeduncular fossa. Besides, other anomalies were found, such as: laryngeal split, abnormal pulmonary lobation, renal agenesis or dysplasia, shorts fourth metacarpals, nail dysplasia, multiple mouth frenulum, hypoadrenalism, congenital cardiomyopathy and intrauterine growth retardation. Every case was sporadic, the chromosome were apparently normal, without consaguinity relations. Several similar, milder and even asymptomatic cases were described later on. Kletter and Biesecker (1992), Topf et all (1993) and Penman Splitt et all (1994), define the disease as dominant autosomal inheritance. Kettler and Biesecker (1992) stated that most cases as sporadic as a result of a gene mutation with variable expressiveness. According to Biesecker et al (1996), an international workshop determined diagnostic criteria to the Syndrome: Hypothalamic Hamartroma and Central Polydactyly; First degree relative with hypothalamic hamartroma and polydactyly; Dominant autosomal parrent inheritance or in a consistent form with germaine mosaicism. The radiological changes are important for differential diagnosis between Pallister-Hall Syndrome and other hamartroma-present diseases. The hypothalamic hamartroma isolated has phenotypical features and causes hormonal disorders such as early puberty. On the MRI (Magnetic resonance imaging) it shows hyperintese sign on attenuated fluid. On the other hand, the Pallister-Hall Syndrome the hamartroma shows itself as a isointense signs along with other deformities as polydactyly, for example. According to Kuo et al (1999), on MRI, the classic hypothalamic hamartroma isn’t calcified, is homogenous and isointense to the grey matter on weight images in T1, and isointense and often hyperintense on weight images in T2. Those findings are pretty distinctive and help distinguish the hypothalamic hamartroma from ordinary lesions, as craniopharyngioma and hypothalamic/opticalchiasmic glioma, observed in children. Case report: The patient ALDV, male, born in 30/12/1995, was referred to evaluation on the Medical Genetic Service from HCPA. At the time, aged one year and 8 months, he was the only son of a young, healthy couple with no consanguinity. The family history of similar cases or other genetic pathologies are unknown. The prenatal happened with no intercurrences, unless the smoking mother. It was a natural birth; Birth Weight: 2kg; High: 42cm; PC: 32cm. APGAR 9. At 8 months, starts an investigation for precocious puberty, and a karyotype was performed in her hometown: 46, XY (normal). He presents convulsive crises since one year old. DNPM: cephalic support when he had 8 months, sat without support at the age of one. Physical examination: Head circumference in the 97th percentile, length above the 97th percentile. Good general condition, dysmorphic, facies with fusion of eyebrows (sinofre), epicanthus, small nose, dysplastic ears with a broad shield, three café-au-lait spots on the body. Presence of pubic hair. Increase in length and diameter of the penis, as well as of the testicles, in relation to chronological age. In the hands, significant brachydactyly with bitateral hexadactyly. In the feet, bilateral hexadactyly. Proximal cutaneous syndactyly between the 2nd and 3rd bilateral arthroids, mainly on the right. Additional exams: Rx of hands and wrists for bone age: 7 years; Chronological Age: 1 year and 10 months. Normal abdominal ultrasound; Computed Tomography of Skull/Magnetic Resonance of Skull: hypothalamic expansive lesion (3 cm), compatible with hamartoma; triventricular hydrocephalus; Cavum septum pellucidum. Endocrinological Evaluation: compatible with precocious puberty of central cause. High resolution karyotype: 46, XY (normal). Computed tomography of the brain: Examination for neurological control, performed on 10/12/2014, 18-year-old patient. It was observed solid nodular formation in the hypothalamic region, hypodense, with well-defined limits, in close contact with the mesencephalon, without impregnation by contrast medium administered intravenously, measuring about 2.9 X 2.4 X 3.0 cm, in the respective laterolateral, anteroposterior and craniocaudal planes, which in correlation with the patient’s clinical history may be related to hypothalamic Hamartoma.