Andrey V Marakhonov

Andrey V Marakhonov
Russian Academy of Medical Sciences | RAMS · Research Centre of Medical Genetics (RCMG)

PhD

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103
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336
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January 2008 - present

Publications

Publications (103)
Article
Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational...
Article
Intellectual disability is a widespread group of diseases with population frequency 1–3%. More than half of intellectual disability cases are due to various genetic causes, including monogenic ones. The paper describes three clinical cases of MED13L-associated intellectual disability with an autosomal dominant inheritance. Novel probably pathogenic...
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Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun. Ai...
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Familial exudative vitreoretinopathy (FEVR)is a rare genetically heterogeneous disease with multiple types of inheritance (autosomal dominant, autosomal recessive, X-linked) and widely varying clinical features. Up to 40 % of cases of FEVR are associated with mutations of the FZD4 gene. Purpose: to investigate the clinical manifestations of FEVR in...
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Aim : to study genotype-phenotype correlations in patients with inherited retinal diseases with mutations in ABCA4 gene in Russian Federation. Patients and methods . 21 patients from Russian population aged from 7 to 51 years old (mean age 20 ± 11 years with best-corrected visual acuity from 0,02 to 0,6 (0,14 ± 0,11) with ABCA4-associated retinopat...
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Pompe disease (OMIM#232300) is an autosomal recessive lysosomal storage disorder caused by mutations in the GAA gene. According to public mutation databases, more than 679 path-ogenic variants have been described in GAA, none of which are associated with mobile genetic elements. In this article, we report a novel molecular genetic cause of Pompe di...
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The issue of point prevalence, cumulative prevalence (CP), and burden of rare hereditary diseases (RHD), comprising 72–80% of the group of rare diseases, is discussed in many reports and is an urgent problem, which is associated with the rapid progress of genetic technology, the identification of thousands of genes, and the resulting problems in so...
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Background Peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders that affect multiple organ systems. Approximately 80% of PBD patients are classifiedin the Zellweger syndrome spectrum, which is generally caused by mutations in the PEX1, PEX6, PEX10, PEX12, or PEX26 genes. Methods We present the clinical c...
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Cystic fibrosis (CF) is a common monogenic disease caused by pathogenic variants in the CFTR gene. The distribution and frequency of CFTR variants vary in different countries and ethnic groups. The spectrum of pathogenic variants of the CFTR gene was previously studied in more than 1,500 CF patients from different regions of the European and North...
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and keywords Congenital aniridia (AN) is a severe autosomal dominant panocular disorder associated with pathogenic variants in the PAX6 gene. Previously, we performed a molecular genetic study of a large cohort of Russian patients with AN and revealed four non-coding nucleotide variants in the PAX6 5′UTR. Additional 14 PAX6-5′UTR variants were also...
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Цель исследования - изучение взаимосвязи полиморфизмов генов, кодирующих структуру регуляторных белков синтеза и деградации экстрацеллюлярного матрикса соединительной ткани, с развитием первичной открытоугольной глаукомы (ПОУГ). Обследовано 144 человека (мужчин - 56, женщин - 88), средний возраст 59,3±6,2, не состоящих в родстве, русской национальн...
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Hereditary nonsyndromic sensorineural hearing loss is a disease in which hearing loss occurs due to damage to the organ of the inner ear, the auditory nerve, or the center in the brain that is responsible for the perception of sound, characterized by wide locus and allelic heterogeneity and different types of inheritance. Given the diversity of pop...
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The purpose : to describe clinical cases of oculodental-digital dysplasia (ODDD, OMIM #164200) with mutation in GJA1 (OMIM 121014) with molecular genetic verification of the diagnosis. Methods . The article describes the clinical case of oculodental-digital dysplasia in a 51 years old patient. Patient underwent full ophthalmic examination including...
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A young boy with multifocal epilepsy with infantile spasms and hypsarrhythmia with minimal organic lesions of brain structures underwent DNA diagnosis using whole‐exome sequencing. A heterozygous amino‐acid substitution p.L519R in a PHACTR1 gene was identified. PHACTR1 belongs to a protein family of G‐actin binding protein phosphatase 1 (PP1) cofac...
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The article describes a clinical case of a 14-year old patient with RDH5 mutations (OMIM *601617) in patient with fundus albipunctatus (OMIM #136880) and characteristic biomarkers of this disease with previously described pathogenic variant of nucleotic sequence in exon 3 of the RDH5 gene (NM_002905.3:c.500G>A), causing a missense change (p.Arg167H...
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Background: Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract-microcornea syndromes. Results: In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocu...
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Background Hereditary ophthalmic pathology is a genetically heterogeneous group of diseases that occur either as an isolated eye disorder or as a symptom of hereditary syndromes (chromosomal or monogenic). Thus, a diagnostic search in some cases of ophthalmic pathology can be time- and cost-consuming. The most challenging situation can arise when p...
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The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical manifestations and complications (the age at CF diagnosis, sweat test, pancreatic status, lung function, microbial infection, body mass index (BMI), the presence of meconium ileus...
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Background: Because of the significant occurrence of "WAGR-region" deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patien...
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Наследственные заболевания сетчатки (НЗС) представляют собой класс офтальмологических болезней, в котором выделяют заболевания с преимущественным поражением палочковой системы и заболевания с преимущественным поражением колбочковой системы, включающие макулярные дистрофии. В представленном сообщении описана структура спектра НЗС в клинически полимо...
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Врожденная аниридия (OMIM#106210) (ВА) - наследственное аутосомно-доминантное заболевание, ассоциированное с внутригенными мутациями гена PAX6 или крупными хромосомными аберрациями с вовлечением региона 11p13 в гетерозиготном состоянии. Проведено изучение особенностей спектра мутаций гена PAX6 и региона 11p13 в когорте пациентов с ВА из России. Обс...
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Исследования наследственной патологии органа зрения на фоне широкой генетической гетерогенности и выраженного клинического полиморфизма затруднены по причине сложности определения очага первичного повреждения. Часто заболевания переднего отрезка глаза являются пусковыми для повреждения заднего отрезка (сетчатки, хориоидеи, зрительного нерва). В пре...
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Снижение остроты зрения при врожденной аниридии связано с дефектом радужной оболочки и комплексом изменений разной степени выраженности других структур глаза (роговица, зрительный нерв, сетчатка и др.). Прогнозирование изменения рефракции - сложная проблема, так как имеются широкие вариации состояния структур и функций глаза с момента рождения и их...
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Наследственная офтальмологическая патология представляет собой генетически неоднородную группу заболеваний, которые проявляются либо как изолированное глазное расстройство, либо как симптом наследственных синдромов (хромосомных или моногенных). Диагностический поиск в некоторых случаях наследственной офтальмологической патологии может быть трудоемк...
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The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital PAX6-associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving...
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WAGRO syndrome is a rare genetic syndrome that includes Wilms tumor, aniridia, genitourinary system abnormalities, mental retardation, and obesity. The syndrome is associated with deletions of the short arm of chromosome 11 (11p), where the PAX6 and WT1 genes are located. We present the clinical case of a 7-year-old boy with aniridia, polar catarac...
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Background Aniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the PAX6 gene or 11p13 chromosomal aberrations encompassing the coding and/or regulatory regions of the PAX6 gene in a heterozygous state. Patients with aniridia display several ocular anomalies including foveal hypoplasia, cataract...
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The distribution and frequency of the CFTR gene mutations vary considerably between countries and ethnic groups. Russians are an East Slavic ethnic groups are native to Eastern Europe. Russians, the most numerous people of the Russian Federation (RF), make about 80% of the population. The aim is to reveal the molecular causes of CF in ethnic Russia...
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Наследственные заболевания нервно-мышечной системы представляют собой обширную группу генетически гетерогенных наследственных болезней, для которых характерен выраженный клинический полиморфизм. В данном сообщении показана целесообразность применения методов высокопроизводительного секвенирования (ВПС) для постановки точного диагноза редких форм на...
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The L138ins mutation, found in Russian cystic fibrosis (CF) patients, is a duplication of three nucleotides (CTA) in exon 4 of the CFTR gene and is categorised as a small in-frame insertion/deletion. As a result, the CFTR protein molecule elongates by one amino acid residue, leucine, at position 138 (codon 138 (CTA)). In accordance with the new nom...
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Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in d...
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Congenital hearing loss is one of the most frequent inherited human pathologies, occurring in 1-2 out of 1000 newborns. X-linked hearing loss occurs in 1-5% of all congenital hearing impairments. The proband (a man) and his affected brother have profound prelingual non-syndromic neurosensory hearing loss. Their parents are healthy. The aim of the s...
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The results of genetic and epidemiological study of monogenic hereditary diseases (HD) among children of the Karachay-Cherkess Republics are presented. The surveyed population comprised 410 368 individuals (Cherkessk and ten rural areas), including 90 739 children (22.11%). The examination was performed following the original protocol for genetic-e...
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WAGR syndrome (OMIM #194072) is a rare genetic disorder that consists of development of Wilms' tumor (nephroblastoma), Aniridia, Genitourinary anomalies, and intellectual disability (mental Retardation). It is associated with WAGR-region deletions in the 11p13 chromosome region. Our previous study of congenital aniridia patients revealed a noticeab...
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On the Back Cover: The back‐cover image is based on the Brief Report Noncompaction cardiomyopathy is caused by a novel in‐frame desmin (DES) deletion mutation within the 1A coiled‐coil rod segment leading to a severe filament assembly defect by Andrey V. Marakhonov et al., DOI: 10.1002/humu.23747.
Article
The generalized results of the genetic and epidemiological study of the genetic structure of various ethnic groups of the Karachay-Cherkess Republic (KChR) through various genetic systems are presented: by the genes causing AD, AR, and X-linked hereditary diseases and by nonbiological parameters estimated by the methods of population statistics (ra...
Article
Ataxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, PNKP-related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous PNKP mutations was c.1123G>T, common i...
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Изучены особенности распространения наследственных болезней (НБ) у населения Карачаево-Черкесской Республики (КЧР). Суммарная численность обследованной выборки - 410 368 человек, что составило более чем 86% от проживающих на территории региона. Оценена отягощенность городского и сельского населения 21 субпопуляции аутосомно-доминантной (АД), аутосо...
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Ataxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, PNKP-related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous PNKP mutations was c.1123G>T, common i...
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Full-text available
Background Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mu...
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Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVH...
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Rationale : Cystic fibrosis (CF; OMIM 219700) is a common hereditary disease caused by mutations in the CFTR gene (OMIM 602421). The distribution and frequencies of the CFTR gene mutations vary considerably between countries and ethnic groups. By now about 11% alleles of the CFTR gene remain unidentified after testing for frequent mutations in the...
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Single nucleotide variants are represented as lines. The height of the line corresponds to the allele frequency. Gross chromosomal copy number variations are shown as arrows. Color corresponds to the mutation type. Complex alleles represented with a clip. Previously reported variants are located above the schematic gene representation. Their names...
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Neurodegeneration with brain iron accumulation type 4 (NBIA4) also known as MPAN (mitochondria protein-associated neurodegeneration) is a rare neurological disorder which main feature is brain iron accumulation most frequently in the globus pallidus and substantia nigra. Whole exome sequencing (WES) in a 12-year-old patient revealed 2 variants in t...
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Nucleotide variants that disrupt normal splicing might be the cause of a large number of diseases. Nevertheless, because of the complexity of splicing regulation, it is not always possible to accurately predict the effect of nucleotide sequence changes on splicing events and mRNA structure. Thereby, a number of newly identified nucleotide variants...
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Study of the hereditary non-syndromic ophthalmological pathology of child population of the Karachay-Cherkess Republic: estimations of genetic load and molecular genetic analysis V.V. Kadyshev1, A.V. Marakhonov1, S.I. Kutsev1,2, R.A. Zinchenko1,3 1 Research Centre of Medical Genetics of the Russian Academy of Medical Sciences, Moscow, Russian Fed...
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The PAX6 gene encodes one of the key embryonic transcription factors and serves as a master regulator of eye and central nervous system morphogenesis in all species of bilaterian animals. The PAX6 protein contains two DNA binding domains: paired and homeobox. To ensure specific regulation of target genes, the domains are able to bind different DNA...
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To describe the population-genetic structure of the Russian population of Karachay-Cherkessia, the database of Compulsory Medical Insurance and marriage records for 1990–2000 were used. The Russian population is characterized by a low birth rate, low endogamy, low inbreeding, and a high level of miscegenation.
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The genetic load and diversity of monogenic hereditary diseases (HD) in the Russian population of Karachay-Cherkess Republic (KCHR), living in 10 administrative and municipal divisions, were studied. The total size of the population surveyed was 410,367 people, including 134,756 Russians. In total, 385 patients from 281 families were registered amo...
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Clinical And Molecular-Genetic Features Of Congenital Aniridia Vasilyeva T. A.1, Voskresenskaya A. A.2, Kadyshev V. V.1, Pozdeyeva N. A.2, Marakhonov A. V.1,3, Zinchenko R. A.1,4 1 Research Center for Medical Genetics, Moscow 2 Cheboksary branch of S. Fyodorov Eye Microsurgery Federal State Institution 3 Moscow Institute of Physics and Technology...
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The diversity and prevalence of hereditary diseases (HDs) among Nogais of the Karachay-Cherkess Republic (KChR) are described. The size of the surveyed KChR population was 387231 individuals, including 3.81% Nogais (14741 individuals). We revealed 36 nosological forms of HDs (110 patients from 81 families): 22 with autosomal dominant (AD) inheritan...
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Here we present a case report of collagen VI related myopathy in a patient, 8 y.o. boy, with intermediate phenotype between severe Ullrich congenital muscular dystrophy and milder Bethlem myopathy. Whole exome sequencing revealed two novel single nucleotide variants in COL6A3 gene: paternal p.Glu2402Ter, resulting in premature translation terminati...
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Abstract⎯This paper estimates the load and nosological spectrum of monogenic hereditary diseases (HDs) in Abazins of the Karachay-Cherkess Republic (KChR), identified in Cherkessk and ten districts, Abazinsky, Ust-Dzhegutinsky, Malokarachaevsky, Karachaevsky, Prikubansky, Khabezsky, Nogaysky, Adyge-Khablsky, Urupsky, and Zelenchuksky. The number of...