Journal articles on the topic 'Aspetti monogenici'
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1
De Rycke, M. "C2 PGD for monogenic diseases: Molecular aspects." Reproductive BioMedicine Online 20 (May 2010): S1. http://dx.doi.org/10.1016/s1472-6483(10)62256-0.
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Spits, Claudia, and Karen Sermon. "PGD for monogenic disorders: aspects of molecular biology." Prenatal Diagnosis 29, no. 1 (December 19, 2008): 50–56. http://dx.doi.org/10.1002/pd.2161.
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Murphy, Rinki. "Monogenic diabetes and pregnancy." Obstetric Medicine 8, no. 3 (June 29, 2015): 114–20. http://dx.doi.org/10.1177/1753495x15590713.
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Monogenic diabetes is frequently mistakenly diagnosed as either type 1 or type 2 diabetes, yet accounts for approximately 1–2% of diabetes. Identifying monogenic forms of diabetes has practical implications for specific therapy, screening of family members and genetic counselling. The most common forms of monogenic diabetes are due to glucokinase ( GCK), hepatocyte nuclear factor ( HNF) -1A and HNF-4A, HNF-1B, m.3243A>G gene defects. Practical aspects of their recognition, diagnosis and management are outlined, particularly as they relate to pregnancy. This knowledge is important for all physicians managing diabetes in pregnancy, given this is a time when previously unrecognised monogenic diabetes may be uncovered with careful attention to atypical features of diabetes misclassified as type 1, type 2, or gestational diabetes.
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Peterkova, V. A., T. L. Kuraeva, S. A. Prokof’ev, A. O. Emel'yanov, E. Yu Zakharova, P. G. Tsygankova, and D. P. Grishina. "MOLECULAR GENETICS AND CLINICAL ASPECTS OF MONOGENIC DIABETES MELLITUS." Annals of the Russian academy of medical sciences 67, no. 1 (January 22, 2012): 81–86. http://dx.doi.org/10.15690/vramn.v67i1.115.
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The paper is dedicated to clinical and laboratory aspects of Diabetes Mellitus non-immune forms, such as neonatal Diabetes Mellitus, Maturity Onset Diabetes of young (MODY), DIDMOAD-syndrome, Wolframe syndrome, Alstrom syndrome and its determinating genes. The analysis of proper clinical results are present in this paper.
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Lachance, Carl-Hugo. "Practical Aspects of Monogenic Diabetes: A Clinical Point of View." Canadian Journal of Diabetes 40, no. 5 (October 2016): 368–75. http://dx.doi.org/10.1016/j.jcjd.2015.11.004.
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Morais, J., H. T. Le, and W. Sprößig. "On some constructive aspects of monogenic function theory in ℝ4." Mathematical Methods in the Applied Sciences 34, no. 14 (August 8, 2011): 1694–706. http://dx.doi.org/10.1002/mma.1474.
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Ballabio, E., A. Bersano, N. Bresolin, and L. Candelise. "Monogenic Vessel Diseases Related to Ischemic Stroke: A Clinical Approach." Journal of Cerebral Blood Flow & Metabolism 27, no. 10 (June 20, 2007): 1649–62. http://dx.doi.org/10.1038/sj.jcbfm.9600520.
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The identification of stroke cases caused by monogenic disorders is important both for therapeutic decisions and genetic counselling, although they represent less than 1% of all stroke patients. The purpose of this review is to summarize genetic, pathological, and clinical features of single-gene disorders related to ischemic stroke. The following monogenic disorders are considered: cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal-recessive arteriosclerosis with subcortical infarcts and leukoencephalopathy, hereditary endotheliopathy with retinopathy, nephropathy, and stroke, Fabry disease, pseudoxanthoma elasticum, Neurofibromatosis type 1, familial MoyaMoya disease, Ehlers-Danlos syndrome type IV, Marfan syndrome. For each monogenic disorder, mode of inheritance, pathophysiological aspects, clinical phenotype, and diagnostic tools are carefully described. Furthermore, the classification of monogenetic disorders is presented according to stroke mechanisms, which include small vessel diseases, large artery diseases, and arterial dissections. This review could be useful to identify specific diagnostic pathways for patients with a suspicion of monogenic disease.
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Kuchinskaya, E. M., E. N. Suspitsyn, and M. M. Kostik. "Genetic aspects of the pathogenesis of systemic lupus erythematosus in children." Modern Rheumatology Journal 14, no. 1 (March 22, 2020): 101–7. http://dx.doi.org/10.14412/1996-7012-2020-1-101-107.
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The paper presents data on the pathogenesis of systemic lupus erythematosus (SLE), and depicts various molecular mechanisms for the development of SLE and lupus-like syndromes. It describes groups of diseases, such as apoptotic defects; NETosis; interferonopathies; complement deficiency; autotolerance disorders associated with mutations in the RAG1/RAG2 genes; hereditary metabolic diseases (prolidase deficiency, deficiency of adenosine deaminase 2; lysinuric protein intolerance; and α-mannosidase deficiency). The table summarizes clinical data on most of the known lupus-like syndromes and their molecular mechanisms.The pathogenesis of many forms of monogenic lupus-like diseases is being studied. The main sign suggesting in favor of the possible monogenic disease in a patient with SLE is its onset in infancy, especially in males. Attention should be also paid to a compromised family history, including to the marriage between close relatives, the resistance of disease to standard therapy, as well as atypical symptoms.
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Tesser, Alessandra, Alessia Pin, Elisabetta Mencaroni, Virginia Gulino, and Alberto Tommasini. "Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain." International Journal of Environmental Research and Public Health 18, no. 11 (May 24, 2021): 5585. http://dx.doi.org/10.3390/ijerph18115585.
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More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology could be fostered by a better understanding of the disease machinery, to develop a rational use of immuno-modulators in clinical trials. In this review, we focus on monogenic disorders with neurological hyper-inflammation/autoimmunity as simplified “models” to correlate immune pathology and targeted treatments. The study of monogenic models yields great advantages for the elucidation of the pathogenic mechanisms that can be reproduced in cellular/animal models, overcoming the limitations of biological samples to study. Moreover, monogenic disorders provide a unique tool to study the mechanisms of neuroinflammatory and autoimmune brain damage, in all their manifestations. The insight of clinical, pathological, and therapeutic aspects of the considered monogenic models can impact knowledge about brain inflammation and can provide useful hints to better understand and cure some neurologic multifactorial disorders.
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Orlando, Francesca, Germana Nardini, and Daniele De Brasi. "Le malattie autoinfiammatorie: aspetti patogenetici e clinici (Prima parte)." QUADERNI ACP 29, no. 3 (2022): 128. http://dx.doi.org/10.53141/qacp.2022.128-132.
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Autoinflammatory diseases (AIDs) are a family of rare medical entities, characterized by sterile systemic inflammatory episodes caused by exaggerated activation of the innate immune system, for which the pathogenic role of autoantibodies, B or T cells is less relevant. During the past 20 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. Proteins encoded by these genes are involved in the regulatory pathways of inflammation and they are mostly expressed in cells of the innate immune system. Since symptoms can overlap within this rapidly expanding disease category, accurate genetic diagnosis is extremely important to start early targeted treatment and to prevent clinically significant or life-threatening complications. On the other hand, detection of more and more genetic variants makes interpretation of results more complicated, and often a genetic diagnosis is not achieved. Thus, the clinical picture represents the starting point for establishing an effective therapy when genetic data are not sufficient or inconclusive. Biologic agents blocking cytokines action have proved to be dramatically effective in a lot of patients.
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Golukhova, E. Z., O. I. Gromova, R. A. Shomahov, N. I. Bulaeva, and L. A. Bockeria. "Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside." Acta Naturae 8, no. 2 (June 15, 2016): 62–74. http://dx.doi.org/10.32607/20758251-2016-8-2-62-74.
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The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called sudden cardiac death (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator).
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Marklová, Eliška. "Genetic Aspects of Diabetes Mellitus." Acta Medica (Hradec Kralove, Czech Republic) 44, no. 1 (2001): 3–6. http://dx.doi.org/10.14712/18059694.2019.79.
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Practically all types of diabetes mellitus (DM) result from complex interactions of genetic and environmental factors. Multifactorial and polygenic Type 1 DM is strongly influenced by genes controlling the immune system, mainly HLA-DQ and DR. In addition to this, many other predisposition loci, interacting with each other, have some influence on susceptibility to DM. Heterogeneous Type 2 DM, accounting for about 85 % of all diabetic patients, is supposed to be induced by multiple genes defects involved in insulin action and/or insulin secretion. Other genetically influenced traits like obesity and hyperlipidemia are strongly associated with the Type 2. The group called Other specific types of DM include monogenic forms MODY 1-5 and many various subtypes of the disease, where the specific gene mutations have been identified. Both genetic and intrauterine environmental influences are likely to contribute to the abnormalities defined as Gestational DM.
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Tyrtova, Ludmila Viktorovna, Natalja Vladimirovna Parshina, and Kristina Vladimirovna Skobeleva. "Genetic and Epigenetic Aspects of Obessity and Metabolic Syndrom in Child." Pediatrician (St. Petersburg) 4, no. 2 (June 15, 2013): 3–11. http://dx.doi.org/10.17816/ped423-11.
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In a review article analyzes the role of heredity in the occurrence of obesity and metabolic syndrome. Debut of hyperphagia and severe obesity from early childhood are typical for monogenic forms and syndromes. Many nonspecific candidate-genes in combination form a polygenic basis for the accumulation of excess body fat, especially under the influence of irrational diet and low physical activity. Examined the role of epigenetic factors in the individual genetic variants in fetus, predisposing to obesity and metabolic syndrome after birth. Discuss the possibilities of early prevention of obesity and metabolic syndrome.
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Prityko, A. G., N. V. Chebanenko, P. L. Sokolov, V. P. Zykov, O. V. Klimchuk, and I. V. Kanivets. "Genetic Aspects of Pathogenesis of Congenital Spastic Cerebral Paralysis." Acta Biomedica Scientifica 4, no. 3 (July 17, 2019): 28–39. http://dx.doi.org/10.29413/abs.2019-4.3.4.
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Congenital spastic cerebral palsy (СР) is a large group of non-progressive disorders of the nervous system. The basis of the pathogenesis of these conditions is considered the impact of many factors. The clinical diversity of the disease and the syndromic principle of classification determine the existing uncertainties in the diagnosis of these diseases. The multifactorial nature of the underlying brain lesions is obvious and beyond doubt. The volume of information accumulated to date does not allow one to exclude the role and significance of the direct effect of acute asphyxiation in childbirth on a fetus normally formed during pregnancy, the role of infectious brain lesions, and disorders of neuronal migration. It is impossible to ignore the dependence of the clinical picture of the disease on what stage of ontogenesis the impact of the damaging agent occurs. As one of the pathogenetic factors, the genetic determinism of the phenotype of the clinical picture of a disease is fairly considered. This review focuses on the genetic aspects of the pathogenesis of this pathology. The information on monogenic mechanisms of inheritance is analyzed in detail. Such genetically determined mechanisms of pathogenesis as the inheritance of prerequisites for brain trauma in the perinatal period are considered separately. The new clinically significant variants of chromosomal mutations found in patients with CР are reviewed in detail, the evidence of the influence of genetic factors on the development of cerebral palsy in the absence of a pronounced monogenic cause of the disease, obtained through twin studies, is reviewed. Lit search of polymorphisms markers of predisposition to the development of cerebral palsy genes of the folate cycle, genes of glutamate receptors, the gene of apolipoprotein and of the gene for the transcription factor of oligodendrocytes (OLIG2) in Detail the role of epigenetic effects on the activity of genes coding for mitochondrial proteins.
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Arning, Larissa. "The search for modifier genes in Huntington disease – Multifactorial aspects of a monogenic disorder." Molecular and Cellular Probes 30, no. 6 (December 2016): 404–9. http://dx.doi.org/10.1016/j.mcp.2016.06.006.
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Petchesi, Codruța Diana, Gabriela Ciavoi, Claudia Jurca, Romana Vulturar, and Marius Bembea. "Bioethical aspects in type I neurofibromatosis." Romanian Journal of Pediatrics 70, no. 3 (September 30, 2021): 169–72. http://dx.doi.org/10.37897/rjp.2021.3.1.
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Type I neurofibromatosis is one of the most common monogenic disorders, being caused by abnormalities of the neurofibromin gene on chromosome 17. About half of the cases are inherited, respecting the autosomal dominant inheritance criteria, the rest are de novo cases. The clinical manifestations are multisystemic and are progressively installed, presenting inter- and intra-familial variability of clinical expression. The hereditary nature, impaired quality of life and lethal potential identify numerous and various ethical dilemmas in the diagnosis, monitoring and treatment of neurofibromatosis type 1. Variable expressiveness and multisystemic clinical manifestations determine the unpredictable evolutionary character, associating bio-ethical dilemmas necessary to be managed in the clinical context of the disease. As a clinical applicability, we conclude that some of these problems could be avoided by informing and educating affected families about the disease, by increasing confidence in specialized services and by using molecular techniques in order to know as accurately as possible the genotype-phenotype correlation.
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Di Donato, Giulia, Debora Mariarita d’Angelo, Luciana Breda, and Francesco Chiarelli. "Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives." International Journal of Molecular Sciences 22, no. 12 (June 14, 2021): 6360. http://dx.doi.org/10.3390/ijms22126360.
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Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.
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Piras, Doloretta, Nicola Lepori, Gianfranca Cabiddu, and Antonello Pani. "How Genetics Can Improve Clinical Practice in Chronic Kidney Disease: From Bench to Bedside." Journal of Personalized Medicine 12, no. 2 (January 31, 2022): 193. http://dx.doi.org/10.3390/jpm12020193.
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Chronic kidney disease (CKD) is considered a major global health problem with high socio-economic costs: the risk of CKD in individuals with an affected first degree relative has been found to be three times higher than in the general population. Genetic factors are known to be involved in CKD pathogenesis, both due to the possible presence of monogenic pathologies as causes of CKD, and to the role of numerous gene variants in determining susceptibility to the development of CKD. The genetic study of CKD patients can represent a useful tool in the hands of the clinician; not only in the diagnostic and prognostic field, but potentially also in guiding therapeutic choices and in designing clinical trials. In this review we discuss the various aspects of the role of genetic analysis on clinical management of patients with CKD with a focus on clinical applications. Several topics are discussed in an effort to provide useful information for daily clinical practice: definition of susceptibility to the development of CKD, identification of unrecognized monogenic diseases, reclassification of the etiological diagnosis, role of pharmacogenetics.
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Соловьёва, Е. В., Л. П. Назаренко, Л. И. Минайчева, and А. В. Светлаков. "Preimplantation genetic diagnosis (testing) for monogenic disorders: indications and ethics." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 3() (March 29, 2019): 13–25. http://dx.doi.org/10.25557/2073-7998.2019.03.13-25.
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Преимплантационная генетическая диагностика (тестирование) (ПГД/ПГТ) моногенных заболеваний направлена преимущественно на предотвращение рождения ребенка с наследственным заболеванием посредством обследования эмбрионов до имплантации в лечебном цикле ЭКО (экстракорпорального оплодотворения). Строгим показанием для ПГД генной болезни служит высокий риск рождения ребенка с тяжелой формой многогенного заболевания при отсутствии противопоказаний и ограничений. С расширением показаний для ПГД и возможностей генетического тестирования возникают вопросы по нормативному регулированию и этической ответственности врача при проведении процедуры. Этические вопросы возникают, когда генетический риск ниже показателя, расцениваемого как высокий, заболевание не может быть однозначно отнесено к тяжелым, а также при рассмотрении возможности переноса аномального эмбриона. Этические аспекты ПГД рассмотрены с точки зрения базовых этических принципов: пользы и непричинения вреда, автономии, справедливости. В сравнении с пренатальной диагностикой, реализация этих принципов при ПГД сталкивается с рядом дополнительных сложных вопросов. Ценность эмбрионов человека, вероятность оставить супружескую пару без детей должны соотноситься с действительным риском и тяжестью возможного заболевания. Preimplantation genetic diagnosis/testing (PGD/PGT) for monogenic disorders is directed on prevention of the birth of the child with a hereditary disorders by means of testing embryos before implantation in IVF (in vitro fertilization). The high risk of severe form of a single gene disease is a strict medical indication for PGD for monogenic disorders at condition of contraindications and restrictions lack. Extension of PGD indications and genetic testing opportunities raises questions on standard regulation and ethical responsibility. Ethical questions are happening if a genetic risk is lower than the «high» or the disease cannot be classified as serious and if abnormal embryo transfer is proposed. Ethical aspects of PGD are considered in terms of basic ethical principles: beneficence, non-maleficence, autonomy and justice. In comparison with prenatal diagnostics, realization of these principles at PGD faces a number of additional difficult questions. The value of the human embryos and probability to have no children has to correspond to the valid risk and severity of a possible disease.
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Ouafidi, B., O. Wajih, F. Elmiski, H. Kiram, M. Jalal, A. Lamrissi, K. Fichtali, and S. Bouhya. "SYNDROME DE MECKEL GRUBER: A PROPOS DUN CAS RARE." International Journal of Advanced Research 9, no. 06 (June 30, 2021): 365–69. http://dx.doi.org/10.21474/ijar01/13023.
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Meckel-Gruber syndrome is a monogenic congenital disorder characterized by occipital encephalocele, polydactyly, and polycystic kidneys. This syndrome is incompatible with life. We report a case diagnosed on fetal ultrasound at a gestational age of 22 SA and 6 days, presenting the clinical triad of Meckel-Gruber syndrome. A medical termination of the pregnancy was indicated. From this rare case, and through a review of the literature, we will discuss the different clinical, ultrasound and prognostic aspects of this rare pathology.
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Goryainova, A. V., P. V. Shumilov, N. Yu Kashirskaya, and S. Yu Semykin. "THE ROLE OF CONNECTIVE TISSUE DYSPLASIA IN CHILDREN’S CYSTIC FIBROSIS. CLINICAL AND GENETIC ASPECTS." Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) 63, no. 5 (November 20, 2018): 20–28. http://dx.doi.org/10.21508/1027-4065-2018-63-5-20-28.
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The article considers the issue of cystic fibrosis – a monogenic autosomal recessive disease. It describes the history of the CFTR gene discovery, the further search for modifier genes to explain the variability of the clinical manifestations of cystic fibrosis. The review discusses problems of connective tissue dysplasia and somatic pathology, which is formed due to the connective tissue dysmorphogenesis in patients with cystic fibrosis; and also the article contains justification for the connection between the formation of severe fibrosis of the lungs and liver and the presence of clinical and genetic markers of connective tissue dysplasia. The author assumes that the clinical and genetic polymorphisms of connective tissue influence the course of cystic fibrosis, formation of bronchiectasis, interstitial pneumofibrosis, cystic fibrosis dysplasia, liver fibrosis and cirrhosis.
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Deteșan, Oana, Lucia Mihaela Custură, Brigitta Irén Kovács, Reka Annamaria Schmiedt, and Mariana Cornelia Tilinca. "Current Perspectives in MODY Management—A Narrative Review." Timisoara Medical Journal 2021, no. 2 (December 24, 2021): 1. http://dx.doi.org/10.35995/tmj20210204.
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Maturity-onset diabetes of the young (MODY) is associated with familially inherited monogenic diabetes. It is characterized by genetic mutations leading to pancreatic β-cell dysfunction and subsequent insulin production. Clinical features of MODY include young-onset hyperglycemia associated with a lack of beta cell autoimmunity or insulin resistance. Glucose-lowering agents are the main therapeutic options for MODY. In this review, we have outlined the particular aspects of the most common types of MODY in order to assist clinical practitioners in this field.
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Caso, Francesco, Donato Rigante, Antonio Vitale, Orso Maria Lucherini, Luisa Costa, Mariangela Atteno, Adele Compagnone, et al. "Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues." International Journal of Rheumatology 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/513782.
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Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.
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Whitfield, Amanda J., P. Hugh R. Barrett, Frank M. van Bockxmeer, and John R. Burnett. "Lipid Disorders and Mutations in the APOB Gene." Clinical Chemistry 50, no. 10 (October 1, 2004): 1725–32. http://dx.doi.org/10.1373/clinchem.2004.038026.
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Abstract Background: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles. Content: The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo- and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described. Summary: Missense mutations in the LDL-receptor-binding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.
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Kireeva, Victoria Vladimirovna, Svetlana Aleksandrovna Lepekhova, Lyubov Nazirovna Mansurova, and Saryuna Chingisovna Dugarova. "EPIGENETIC AND MOLECULAR AND GENETIC ASPECTS OF OBESITY AS A RISK FACTOR OF CARDIOVASCULAR CATASTROPHES." EurasianUnionScientists 5, no. 7(76) (August 20, 2020): 39–44. http://dx.doi.org/10.31618/esu.2413-9335.2020.5.76.926.
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The review provides current information of obesity in the pathogenesis of cardiovascular diseases the leading cause of death. Showing the genetic basis for the development of metabolic syndrome. The question of external influence on genes, mutations in which lead to the development of obesity is determined. The question of the possible role of exogenous destroyers in the development of metabolic syndrome is considered. The main genes involved in monogenic and polygenic variants of obesity are identified. The review shows that to prevent the development of metabolic syndrome, it is necessary to form risk groups and to take mandatory preventive activity in these groups. Pathogenetic significance determines the attention of clinicians to this pathology, and the molecular and genetic aspects of formation the cardiovascular diseases dictate the need for personalized medicine to predict and prevent, and pharmacogenetics to correct obesity, metabolic syndrome and the cardiovascular system as a whole.
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Martins Junior, Carlos Roberto, Fabrício Castro de Borba, Alberto Rolim Muro Martinez, Thiago Junqueira Ribeiro de Rezende, Iscia Lopes Cendes, José Luiz Pedroso, Orlando Graziani Povoas Barsottini, and Marcondes Cavalcante França Júnior. "Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1." Arquivos de Neuro-Psiquiatria 76, no. 8 (August 2018): 555–62. http://dx.doi.org/10.1590/0004-282x20180080.
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ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.
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Zhogova, O. V., N. V. Lagunova, S. V. Ivanovsky, S. O. Salugina, and M. M. Kostik. "Familial Mediterranean fever in the Republic of Crimea: a description of a series of cases with an analysis of historical and ethnographic aspects of the disease." Rheumatology Science and Practice 57, no. 3 (July 11, 2019): 339–44. http://dx.doi.org/10.14412/1995-4484-2019-339-344.
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Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease with a high prevalence in some countries. The carriers of the MEFV gene causing FML are Jews, Armenians, Turks, Arabs and other nationalities of Mediterranean origin. Crimean Tatars are one of the nations that inhabit the Crimean peninsula, who do not formally belong to Mediterranean populations. Until 2016, there were no data on FMF in Crimea among the Crimean Tatar population; however, 15 new cases of FMF have been diagnosed in the Republic of Crimea in the past 2 years. The paper provides data on FML patients and information about the ethnic origin of the Crimean Tatars, explaining the possible origin of mutant alleles in the population.
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Penyaeva, Elena V. "Genetic aspects of Ebstein anomaly and related heart diseases." Annals of the Russian academy of medical sciences 76, no. 1 (April 12, 2021): 67–74. http://dx.doi.org/10.15690/vramn1228.
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Ebstein anomaly is a congenital heart disease, which is characterized by the presence of atrialized portion of the right ventricle, formed as a result of displacement of the tricuspid valve leaflets into the right ventricle and their partial adherence to the underlying myocardium. Atrialized portion in the right ventricle occupies the space between the fibrous annulus of the right atrioventricular orifice and the functional annulus of tricuspid valve, which represents a zone of closure of free (non-adherent to the underlying myocardium) edges of its leaflets. Ebstein anomaly is very rarely isolated, and can be combined with a number of heart diseases and be an integral part of hereditary syndromes. Currently, the role of genetic research in the investigation of the etiology of human diseases as well as understanding of the relationship between different diseases is increasing. The review presents literature data on the combination of Ebstein anomaly with other heart diseases (congenital heart diseases, Wolf-Parkinson-White syndrome, cardiomyopathies, including left ventricular noncompaction), inter alia, within the scope of hereditary syndromes (Noonan syndrome, 8p deletion syndrome, 18q deletion syndrome, 1p36 deletion syndrome, Pierre Robin syndrome). Genetic factors (gene and chromosomal mutations) lying at the core of Ebstein anomaly, as well as heart diseases combined with it, are highlighted. The analysis of published data suggests that Ebstein anomaly is a monogenic disease, and is characterized by allelic and locus genetic heterogeneity. The combination of Ebstein anomaly with other heart diseases is based on their genetic linkage.
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Müllenbach, Roman, Susanne N. Weber, and Frank Lammert. "Nuclear Receptor Variants in Liver Disease." Journal of Lipids 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/934707.
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This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment.
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Baz, Baz, Jean-Pierre Riveline, and Jean-François Gautier. "ENDOCRINOLOGY OF PREGNANCY: Gestational diabetes mellitus: definition, aetiological and clinical aspects." European Journal of Endocrinology 174, no. 2 (February 2016): R43—R51. http://dx.doi.org/10.1530/eje-15-0378.
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Gestational diabetes (GDM) is defined as a glucose intolerance resulting in hyperglycaemia of variable severity with onset during pregnancy. This review aims to revisit the pathogenesis and aetiology of GDM in order to better understand its clinical presentation and outcomes. During normal pregnancy, insulin sensitivity declines with advancing gestation. These modifications are due to placental factors, progesterone and estrogen. In a physiological situation, a compensatory increase in insulin secretion maintains a normal glucose homeostasis. GDM occurs if pancreatic β-cells are unable to face the increased insulin demand during pregnancy. GDM is most commonly a forerunner of type 2 diabetes (T2D) – the most prevalent form of diabetes. These women share similar characteristics with predisposed subjects to T2D: insulin resistance before and after pregnancy, and carry more T2D risk alleles. Auto-immune and monogenic diabetes are more rare aetiologies of GDM. Adverse pregnancy outcomes of GDM are mainly related to macrosomia caused by fetal hyperinsulinism in response to high glucose levels coming from maternal hyperglycaemia. Screening recommendations and diagnosis criteria of GDM have been recently updated. High risk patients should be screened as early as possible using fasting plasma glucose, and if normal, at 24–28 weeks of gestation using 75 g oral glucose tolerance test. The treatment of GDM is based on education with trained nurses and dieticians, and if necessary insulin therapy.
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Berta, Eszter, Noémi Zsíros, Miklós Bodor, István Balogh, Hajnalka Lőrincz, György Paragh, and Mariann Harangi. "Clinical Aspects of Genetic and Non-Genetic Cardiovascular Risk Factors in Familial Hypercholesterolemia." Genes 13, no. 7 (June 27, 2022): 1158. http://dx.doi.org/10.3390/genes13071158.
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Familial hypercholesterolemia (FH) is the most common monogenic metabolic disorder characterized by considerably elevated low-density lipoprotein cholesterol (LDL-C) levels leading to enhanced atherogenesis, early cardiovascular disease (CVD), and premature death. However, the wide phenotypic heterogeneity in FH makes the cardiovascular risk prediction challenging in clinical practice to determine optimal therapeutic strategy. Beyond the lifetime LDL-C vascular accumulation, other genetic and non-genetic risk factors might exacerbate CVD development. Besides the most frequent variants of three genes (LDL-R, APOB, and PCSK9) in some proband variants of other genes implicated in lipid metabolism and atherogenesis are responsible for FH phenotype. Furthermore, non-genetic factors, including traditional cardiovascular risk factors, metabolic and endocrine disorders might also worsen risk profile. Although some were extensively studied previously, others, such as common endocrine disorders including thyroid disorders or polycystic ovary syndrome are not widely evaluated in FH. In this review, we summarize the most important genetic and non-genetic factors that might affect the risk prediction and therapeutic strategy in FH through the eyes of clinicians focusing on disorders that might not be in the center of FH research. The review highlights the complexity of FH care and the need of an interdisciplinary attitude to find the best therapeutic approach in FH patients.
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Zhuravlev, N. M., N. A. Shnayder, and R. F. Nasyrova. "The role of DNA-profiling in predicting anticonvulsant-induced QT prolongation diseases based on pharmacogenetic aspects." Pharmacogenetics and Pharmacogenomics, no. 1 (February 27, 2023): 37–52. http://dx.doi.org/10.37489/2588-0527-2022-1-37-52.
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Anticonvulsants or antiepileptic drugs (AEDs) are widely used for various neurological and psychiatric diseases and are often prescribed for a long period. In this regard, the issue of their safety profile is acute, including risk assessment for the development of life-threatening conditions and adverse drug reactions (ADRs). From the point of view of personalized medicine, it is important to develop an interdisciplinary approach to the development of a new strategy for a personalized approach to predicting AED-induced prolongation of the QT interval as one of the most unfavorable prognostic cardiac ADRs (including sudden death syndrome — SDS). We searched the databases of full-text publications for the period from 2012 to 2022 for keywords and their combinations. We have discovered and systematized monogenic and multifactorial forms of long QT syndrome (LQTS) and candidate genes that slow down AEDs metabolism in the liver. Identification of risk alleles of single nucleotide variants (SNV) of candidate genes predisposing to the development of AED-induced LQTS and SDS will allow adjusting the choice and dosage of these drugs and preventing the development of the ADR, which will improve the quality of life and help prevent SDS in patients with mental and neurological disorders
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Schmitt, Lauren, Rebecca Shaffer, David Hessl, and Craig Erickson. "Executive Function in Fragile X Syndrome: A Systematic Review." Brain Sciences 9, no. 1 (January 16, 2019): 15. http://dx.doi.org/10.3390/brainsci9010015.
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Executive function (EF) supports goal-directed behavior and includes key aspects such as working memory, inhibitory control, cognitive flexibility, attention, processing speed, and planning. Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and is phenotypically characterized by EF deficits beyond what is expected given general cognitive impairments. Yet, a systematic review of behavioral studies using performance-based measures is needed to provide a summary of EF deficits across domains in males and females with FXS, discuss clinical and biological correlates of these EF deficits, identify critical limitations in available research, and offer suggestions for future studies in this area. Ultimately, this review aims to advance our understanding of the underlying pathophysiological mechanisms contributing to EF in FXS and to inform the development of outcome measures of EF and identification of new treatment targets in FXS.
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Timasheva, Ya R., Zh R. Balkhiyarova, and O. V. Kochetova. "Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19." Problems of Endocrinology 67, no. 4 (September 16, 2021): 20–35. http://dx.doi.org/10.14341/probl12775.
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Obesity affects over 700 million people worldwide and its prevalence keeps growing steadily. The problem is particularly relevant due to the increased risk of COVID-19 complications and mortality in obese patients. Obesity prevalence increase is often associated with the influence of environmental and behavioural factors, leading to stigmatization of people with obesity due to beliefs that their problems are caused by poor lifestyle choices. However, hereditary predisposition to obesity has been established, likely polygenic in nature. Morbid obesity can result from rare mutations having a significant effect on energy metabolism and fat deposition, but the majority of patients does not present with monogenic forms. Microbiome low diversity significantly correlates with metabolic disorders (inflammation, insulin resistance), and the success of weight loss (bariatric) surgery. However, data on the long-term consequences of bariatric surgery and changes in the microbiome composition and genetic diversity before and after surgery are currently lacking. In this review, we summarize the results of studies of the genetic characteristics of obesity patients, molecular mechanisms of obesity, contributing to the unfavourable course of coronavirus infection, and the evolution of their microbiome during bariatric surgery, elucidating the mechanisms of disease development and creating opportunities to identify potential new treatment targets and design effective personalized approaches for the diagnosis, management, and prevention of obesity.
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Revazyan, K. Z., A. N. Meshkov, A. I. Ershova, O. V. Sivakova, and O. M. Drapkina. "Psychosocial, ethical, legal and economic aspects of genetic screening for the carriage of variants that cause the development of monogenic recessive diseases." Profilakticheskaya meditsina 24, no. 2 (2021): 102. http://dx.doi.org/10.17116/profmed202124021102.
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Chaturvedi, Purnima, Rohit Kumar, and Sapna Ratan Shah. "Bio-Mechanical and Bio-Rheological Aspects of Sickle Red Cells in Microcirculation: A Mathematical Modelling Approach." Fluids 6, no. 9 (September 8, 2021): 322. http://dx.doi.org/10.3390/fluids6090322.
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Sickle cell disease (SCD) is an inherited monogenic disease characterized by distorted red blood cells that causes vaso-occlusion and vasculopathy. Presently, electrophoresis of haemoglobin and genotyping are used as routine tests for diagnosis of the SCD. These techniques require specialized laboratories and are expensive. The low-cost microfluidics-based diagnostic tool holds a great attention for screening of red blood cell (RBC) deformability. In the present study, lubrication theory has been applied in order to develop a biomechanical model of microcirculation with altered rheological properties of sickle blood in the capillary, which is smaller in size compared to the cell diameter, to explain the multifactorial nature and pathogenesis of vaso-occlusion in SCD. The governing equations have been solved analytically for realistic boundary conditions and simulated using MATLAB. We found that the axial velocity of the cell decreases with a decrease in deformability and compliance. The height of the lubricating film predicts deformation of the cell with respect to local pressure in the microcirculation. Leak back and drag force depend non-linearly on the deformed cell radius with varying viscosity of the plasma and Reynolds number. The modelling predictions of this study is in coherence with experimental results. The analyzed parameters provide unique insights with novel possibilities to design a microfluidics-based effective therapeutic intervention for SCD.
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Guja, Cristian, Loreta Guja, and Constantin Ionescu-Tîrgovişte. "Neonatal Diabetes – From Gene Discovery yo Clinical Practice Changes." Romanian Journal of Diabetes Nutrition and Metabolic Diseases 20, no. 3 (September 1, 2013): 343–52. http://dx.doi.org/10.2478/rjdnmd-2013-0034.
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Abstract Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases
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Pedro-Botet, Juan, Elisenda Climent, and David Benaiges. "Familial Hypercholesterolemia: Do HDL Play a Role?" Biomedicines 9, no. 7 (July 13, 2021): 810. http://dx.doi.org/10.3390/biomedicines9070810.
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Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects.
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Grumett, David. "Cult books revisited: Pierre Teilhard de Chardin’s The Phenomenon of Man." Theology 122, no. 6 (November 2019): 404–11. http://dx.doi.org/10.1177/0040571x19872102.
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Teilhard’s The Phenomenon of Man was posthumously published and has been retranslated as The Human Phenomenon. It presents humankind in unity with an evolving world, locates parts in relation to the whole, and balances the perspectives of the outside and the inside. Key aspects include the tangential–radial energy distinction, axes of evolution, the noosphere and personalization. Although Teilhard regarded it as a scientific work, he leaves space for the theological notions of ensoulment, monogenism and the supernatural, and derives his hypothesis that Omega is a point of evolutionary convergence from Scripture. Today, Teilhard’s cosmic vision appeals to some and the global context he defines is ecologically significant, but his dense theorizing may obscure or detract from basic elements of Christian belief.
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Sgobbi de Souza, Paulo Victor, Bruno de Mattos Lombardi Badia, Eduardo Augusto Gonçalves, Igor Braga Farias, Wladimir Bocca Vieira de Rezende Pinto, and Acary Souza Bulle Oliveira. "Hereditary inclusion body myopathy: a clinical and genetic review." Revista Neurociências 28 (July 24, 2020): 1–23. http://dx.doi.org/10.34024/rnc.2020.v28.10569.
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Introduction. Inclusion body myositis represents the most common acquired myopathy in clinical practice in patients over 50 years old. Despite classical approach to this myopathy as an inflammatory disorder, a muscle degenerative disorder is now considered the main mechanism linked to these vacuolar myopathies. Hereditary presentations, although quite rare, represent an expanding and underrecognized group in clinical practice. Objective. perform a structured review of the current literature regarding hereditary inclusion body myopathies. Method. review of U.S. NLM PubMed and MEDLINE database of original articles, case reports, case series and review articles including the terms “inclusion body myositis” OR “inclusion body myopathy” AND “genetics” OR “hereditary”. Results. We present in this article a wide review regarding the main clinical, imaging, pathophysiological, genetic and therapeutic aspects related to hereditary myopathies linked to seven different clinical and genetic presentations (GNE, MATR3, VCP, SQSTM1, MYH2, HNRNPA2B1 and HNRNPA1). Conclusion. Hereditary inclusion body myopathy is associated with at least 7 distinct clinic and genetic monogenic forms.
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Mabillard, Holly, and John A. Sayer. "The Molecular Genetics of Gordon Syndrome." Genes 10, no. 12 (November 29, 2019): 986. http://dx.doi.org/10.3390/genes10120986.
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Gordon syndrome is a rare inherited monogenic form of hypertension, which is associated with hyperkalaemia and metabolic acidosis. Since the recognition of this predominantly autosomal dominant condition in the 1960s, the study of families with Gordon syndrome has revealed four genes WNK1, WNK4, KLHL3, and CUL3 to be implicated in its pathogenesis after a phenotype–genotype correlation was realised. The encoded proteins Kelch-like 3 and Cullin 3 interact to form a ring-like complex to ubiquitinate WNK-kinase 4, which, in normal circumstances, interacts with the sodium chloride co-symporter (NCC), the epithelial sodium channel (ENaC), and the renal outer medullary potassium channel (ROMK) in an inhibitory manner to maintain normokalaemia and normotension. WNK-kinase 1 has an inhibitory action on WNK-kinase 4. Mutations in WNK1, WNK4, KLHL3, and CUL3 all result in the accumulation of WNK-kinase 4 and subsequent hypertension, hyperkalaemia, and metabolic acidosis. This review explains the clinical aspects, disease mechanisms, and molecular genetics of Gordon syndrome.
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Nasimuzzaman, Md, and Punam Malik. "Role of the coagulation system in the pathogenesis of sickle cell disease." Blood Advances 3, no. 20 (October 22, 2019): 3170–80. http://dx.doi.org/10.1182/bloodadvances.2019000193.
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AbstractSickle cell disease (SCD) is an inherited monogenic red blood cell disorder affecting millions worldwide. SCD causes vascular occlusions, chronic hemolytic anemia, and cumulative organ damage such as nephropathy, pulmonary hypertension, pathologic heart remodeling, and liver necrosis. Coagulation system activation, a conspicuous feature of SCD that causes chronic inflammation, is an important component of SCD pathophysiology. The key coagulation factor, thrombin (factor IIa [FIIa]), is both a central protease in hemostasis and thrombosis and a key modifier of inflammation. Pharmacologic or genetic reduction of circulating prothrombin in Berkeley sickle mice significantly improves survival, ameliorates vascular inflammation, and results in markedly reduced end-organ damage. Accordingly, factors both upstream and downstream of thrombin, such as the tissue factor–FX complex, fibrinogen, platelets, von Willebrand factor, FXII, high-molecular-weight kininogen, etc, also play important roles in SCD pathogenesis. In this review, we discuss the various aspects of coagulation system activation and their roles in the pathophysiology of SCD.
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Dehghani, Anisa, and Hulya Karatas. "Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology." Current Neuropharmacology 17, no. 10 (September 13, 2019): 961–73. http://dx.doi.org/10.2174/1570159x17666190513085013.
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Migraine, an extremely disabling neurological disorder, has a strong genetic component. Since monogenic migraines (resulting from mutations or changes in a single gene) may help researchers discover migraine pathophysiology, transgenic mice models harboring gene mutations identified in Familial Hemiplegic Migraine (FHM) patients have been generated. Studies in these FHM mutant mice models have shed light on the mechanisms of migraine and may aid in the identification of novel targets for treatment. More specifically, the studies shed light on how gene mutations, hormones, and other factors impact the pathophysiology of migraine. The models may also be of relevance to researchers outside the field of migraine as some of their aspects are relevant to pain in general. Additionally, because of the comorbidities associated with migraine, they share similarities with the mutant mouse models of epilepsy, stroke, and perhaps depression. Here, we review the experimental data obtained from these mutant mice and focus on how they can be used to investigate the pathophysiology of migraine, including synaptic plasticity, neuroinflammation, metabolite alterations, and molecular and behavioral mechanisms of pain.
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Fedorov, E. S., and S. O. Salugina. "Familial Mediterranean fever (periodic disease): history or a real problem." Modern Rheumatology Journal 12, no. 3 (September 16, 2018): 61–69. http://dx.doi.org/10.14412/1996-7012-2018-3-61-69.
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The review is devoted to the most common monogenic autoinflammatory disease – familial Mediterranean fever (FML) caused by MEFV gene mutation that occurs mainly in the representatives of certain ethnic groups and manifests itself as recurrent 6–72-hour attacks of pyretic fever accompanied by the phenomena of aseptic peritonitis, pleurisy, arthritis, and inflammatory rash. The disease can lead to a life-threatening complication, such as amyloidosis. FML is noted to be comorbid with a number of other inflammatory diseases: systemic vasculitis, chronic joint inflammatory diseases, and inflammatory bowel diseases. Emphasis is laid on the therapy aspects set out in the 2016 EULAR guidelines. The mainstay of treatment for FML is colchicine that prevents recurrences of the disease, minimizes the risk of amyloidosis, and should be prescribed immediately, once diagnosed. The paper deals with the definition of colchicine resistance that is observed in 5–10% of patients. Biological agents, among which interleukin-1 are most preferred, are now used to treat this category of patients. The high efficacy of these agents in patients with FML has been confirmed in randomized controlled studies.
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Cavallieri, Francesco, Rubens G. Cury, Thiago Guimarães, Valentina Fioravanti, Sara Grisanti, Jessica Rossi, Edoardo Monfrini, et al. "Recent Advances in the Treatment of Genetic Forms of Parkinson’s Disease: Hype or Hope?" Cells 12, no. 5 (February 27, 2023): 764. http://dx.doi.org/10.3390/cells12050764.
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Parkinson’s disease (PD) is a multifarious neurodegenerative disease. Its pathology is characterized by a prominent early death of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies with aggregated α-synuclein. Although the α-synuclein pathological aggregation and propagation, induced by several factors, is considered one of the most relevant hypotheses, PD pathogenesis is still a matter of debate. Indeed, environmental factors and genetic predisposition play an important role in PD. Mutations associated with a high risk for PD, usually called monogenic PD, underlie 5% to 10% of all PD cases. However, this percentage tends to increase over time because of the continuous identification of new genes associated with PD. The identification of genetic variants that can cause or increase the risk of PD has also given researchers the possibility to explore new personalized therapies. In this narrative review, we discuss the recent advances in the treatment of genetic forms of PD, focusing on different pathophysiologic aspects and ongoing clinical trials.
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Horton, Rachel, and Anneke M. Lucassen. "The moral argument for heritable genome editing requires an inappropriately deterministic view of genetics." Journal of Medical Ethics 45, no. 8 (March 12, 2019): 526–27. http://dx.doi.org/10.1136/medethics-2019-105390.
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Gyngell and colleagues consider that the recent Nuffield Council report does not go far enough: heritable genome editing (HGE) is not just justifiable in a few rare cases; instead, there is a moral imperative to undertake it. We agree that there is a moral argument for this, but in the real world it is mitigated by the fact that it is not usually possible to ensure a better life. We suggest that a moral imperative for HGE can currently only be concluded if one first buys into an overly deterministic view of a genome sequence, and the role of variation within in it, in the aetiology of the disease: most diseases cannot simply be attributed to specific genetic variants that we could edit away. Multiple, poorly understood genetic and environmental factors interact to influence the expression of diseases with a genetic component, even well understood ‘monogenic’ disorders. Population-level genome analyses are now demonstrating that many genetic ’mutations' are much less predictive than previously thought 1 . Furthermore, HGE might introduce new risks just as it reduces old ones; or remove protections not yet clearly delineated.
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Cordone, Valeria, Alessandra Pecorelli, and Giuseppe Valacchi. "Sirtuins as potential therapeutic targets for mitigating OxInflammation in typical Rett syndrome: plausible mechanisms and evidence." Redox Experimental Medicine 2022, no. 1 (July 1, 2022): R26—R39. http://dx.doi.org/10.1530/rem-22-0004.
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Graphical abstract Abstract Rett syndrome (RTT), a monogenic neurodevelopmental disorder mainly affecting female, is caused by mutations in X-linked MECP2 gene, an ubiquitous epigenetic regulator. In addition to neurological issues, RTT patients show a variety of multisystem manifestations and impairment of different signalling and metabolic pathways, including compromised mitochondrial function, altered redox homeostasis, improper cholesterol metabolism and subclinical inflammation. The sirtuin family (SIRTs), comprising seven members, catalyses the NAD+-dependent deacetylation, ADP-ribosylation and deacylation of a wide range of targets and works as sensors of cellular energetic status. In addition, SIRTs can modulate activities and gene expression of proteins involved in cellular stress responses related to oxidative stress, mitochondrial dysfunctions and inflammation, in both physiological and pathological conditions. Given some shared molecular aspects, herein, we revised the current scientific literature and hypothesized the possible relationship of SIRTs signalling involvement in RTT pathogenesis and OxInflammation. Although further research is needed, uncovering the possible involvement of SIRTs in RTT could reveal new potential pharmacological targets for the disorder. In light of this, SIRT-enhancing compounds could likely represent a new option to be tested as co-adjuvant alternatives to the current therapies.
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Zimmer, Vincent, Roman Liebe, and Frank Lammert. "Nuclear Receptor Variants in Liver Disease." Digestive Diseases 33, no. 3 (2015): 415–19. http://dx.doi.org/10.1159/000371695.
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This snapshot reviews the current state of knowledge on genetic variants of nuclear receptors (NRs) involved in regulating various aspects of liver metabolism. Interindividual differences in responses to diet and other ‘in-' and environmental stressors can be caused by variants in components of the NR regulatory gene network. We recapitulate recent evidence for the application of NRs in genetic diagnosis of monogenic liver disease. Genetic analysis of multifactorial liver diseases, such as nonalcoholic fatty liver disease and diabetes mellitus, pinpoints key players in disease predisposition and progression. In particular, NR1H4 variants have been associated with intrahepatic cholestasis of pregnancy and gallstone disease. Other examples include studies of NR1I2 and NR1I3 polymorphisms in patients with drug-induced liver injury and NR5A2 variation in cholangiocarcinoma. Associations of NR gene variants have been identified in patients with dyslipidemia and other metabolic syndrome-associated traits by genome-wide studies. Evidence from these analyses confirms a role for NR variation in common diseases, linking regulatory networks to complex and variable phenotypes. These new insights into the impact of NR variants offer perspectives for their future use in diagnosis and treatment of common diseases.
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Griessenauer, Christoph J., Sean Farrell, Atom Sarkar, Ramin Zand, Vida Abedi, Neil Holland, Andrew Michael, et al. "Genetic susceptibility to cerebrovascular disease: A systematic review." Journal of Cerebral Blood Flow & Metabolism 38, no. 11 (September 5, 2018): 1853–71. http://dx.doi.org/10.1177/0271678x18797958.
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Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion criteria. Most studies of interest focused on ischemic stroke and cerebrovascular occlusive disease. Large cohort genetic association studies on hemorrhagic cerebrovascular disease were less common. In addition to rare, well-established monogenic conditions with significant risk for cerebrovascular disease, a number of genetic variants are also relevant to cerebrovascular pathogenesis as part of a multifactorial process. The 45 polymorphisms identified were located in genes involved in processes related to endothelial and vascular health (15 (33.4%) variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%) variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2 (4.4%) variants), and other (6 (13.3%) variants). This work represents a comprehensive overview of genetic variants in the exome relevant to ischemic and hemorrhagic stroke pathophysiology.
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Баранова, Е. Е., Г. Ю. Зобкова, and В. Л. Ижевская. "The assessment of ethical aspects of the genetic counseling efficacy in Russian Federation." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 11(220) (November 30, 2020): 39–46. http://dx.doi.org/10.25557/2073-7998.2020.11.39-46.
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Цель исследования: выявить этические проблемы, возникающие в процессе медико-генетического консультирования при использовании современных методов генетического тестирования (полногеномный анализ, расширенный скрининг носителей мутаций). Для исследования была разработана анкета, позволяющая оценить социально-демографические и профессиональные характеристики врача и содержащая вопросы и ситуационные задачи по основным этическим проблемам. В анкетировании приняло участие 30 специалистов разных специальностей, связанных с медицинской генетикой. При назначении генетических тестов врачам было важно помочь супружеским парам иметь здоровых детей. Большинство респондентов считали, что до вступления в брак ответственные люди должны знать, не являются ли они или их партнеры носителями мутаций, приводящих к наследственным заболеваниям, которые могут быть переданы детям. Также большая часть респондентов высказала согласие с необходимостью обязательного скрининга на носительство мутаций наиболее частых моногенных заболеваний и неонатального скрининга на миодистрофию Дюшенна и спинальную мышечную атрофию. Кроме того, специалисты поддерживают необходимость создания этического кодекса врачей-генетиков. В данном пилотном исследовании были выявлены основные векторы этических проблем специалистов медико-генетического профиля, которые требуют углубленного изучения в последующих более масштабных исследованиях. The study aim was to identify ethical problems arising in the process of genetic counseling while using modern methods of genetic testing (WGS, extended carrier screening). A special questionnaire was developed to assess the ethical dilemmas and attitudes of doctors working in the field of medical genetics. The questionnaire consists of 28 complex questions and contains a general part that allows you to evaluate the socio-demographic and professional characteristics of the doctor. The survey was attended by 30 specialists. For doctors it was important to help married couples have healthy children while prescribing genetic tests. The majority of the respondents believed that before marriage, responsible people should know if they or their partners are carriers of mutations that lead to inherited diseases that can be passed on to children. Also, most of the respondents agreed with the need for mandatory screening for the carriage of mutations in the most common monogenic diseases and neonatal screening for Duchenne muscular dystrophy and spinal muscular atrophy. In addition, experts support the creation of an ethical codex for geneticists. In this pilot study, the main vectors of ethical problems of medical and genetic specialists were identified, which require in-depth study in subsequent larger studies.