The data on family history monogenic diseases of the main ethnic groups living in the Republic of Buryatia (Buryatia, Russian). A total of seven people in rural areas (Dzhidinsk, Yeravninsky, Kabansky, Kizhinginsky, Kurumkansky, Kyakhta, Okinsky) and Ulan -Ude . The heterogeneity of the Buryat population of rural areas on the cargo autosomal dominant and X-linked diseases , as well as the presence of differentiation between urban and rural population in this ethnic group loading for autosomal dominant, autosomal recessive and X-linked diseases. Burdened by the rural population of the Buryat for all types of diseases is higher than urban. For Russian, living in rural areas, the differences in the assessment of burdeness obtained for the autosomal dominant and autosomal recessive disease. The present study describes a higher level of loading for autosomal dominant and X-linked disorders Buryat in comparison with Russian.

The paper presents the results of the medical genetic examination of 10 populations of the Karachay-Cherkess Republic (KCR) describing the epidemiology (including molecular epidemiology) of hereditary diseases. Molecular confirmation of diagnosis was performed for 181 patients by PCR, MLPA and Sanger sequencing. Molecular epidemiology of three the most common inherited autosomal recessive diseases (cystic fibrosis, sensorineural hearing loss and phenylketonuria) was studied in main ethnic groups KCR (Karachays, Russians, Cherkess, Abazins, Nogais). The frequencies of the three diseases were estimated according to the newborn screening data: cystic fibrosis - 1:2647 people, sensorineural hearing loss - 1:1551, phenylketonuria - 1:1638. Two rare autosomal dominant diseases were diagnosed in KCR and confirmed with NGS (isolated aniridia and metatropic spondyloepimetaphyseal dysplasia). This allowed to identify novel previously unreported causative mutations in both cases.

Importance. To perform molecular diagnosis in familial case of tuberous sclerosis in Karachay-Cherkess Republic. Objective. To confirm clinical diagnosis of tuberous sclerosis in proband and his relatives. Design, Setting and Participants. High-throughput sequencing (HTS) was used for initial molecular diagnosis in proband. Sanger sequencing was used to confirm high-throughput sequencing data and to determine mutation statusin the family. Results. Recurrent nonsense mutation was identified in proband and his affected relatives. Mutation lead to premature stop codon in 692 codon of TSC1 . Mutation was confirmed in affected relatives of proband. Conclusions and Relevance. Combination of HTS with detailed analysis of clinical data enabled to identify causative mutation in a family with tuberous sclerosis. Mutation co-segregated with the disease in the family.

DiGeorge syndrome (OMIM 188400) and velo-cardio-facial syndrome (VCFS) (OMIM 192430) constitute a group of «CATCH 22», which is characterized by microdeletions of different lengths in the chromosome 22q11.2 region. Microdeletion rate is quite high, and is 1 in 4000 live births in the population, making this disease one of the most common microdeletion syndromes. At the present time to identify microdeletions along with standard high-resolution chromosome analysis methods, comparative genomic hybridization, FISH analysis, fragment analysis and multiplex ligation reaction are used. The advantages of microsatellite analysis are speed, efficiency and cheapness. We present the results of DNA diagnostics on 389 patients, referred to the laboratory with a diagnosis of CATCH 22, using the medical technology which is an effective method of rapid detection of deletions of chromosome 22 sequences by amplification of highly polymorphic microsatellite DNA loci. The diagnostic panel includes STR-markers mapped in a critical region of chromosome 22. Markers D22S264 , D22S1638 , D22S941 , D22S873 , D22S4 , D22S1709 are located in the smallest region of overlap of all deletions identified to date. Diagnosis is carried out on DNA obtained from peripheral blood lymphocytes of patients and their parents. DNA diagnostics is possible to confirm the diagnosis in the case of fetal death or premature death of the child on the formalin-fixed paraffin embedded autopsy material.

A case of osteogenesis imperfecta type 2 in a 20 weeks fetus aborted after prenatal diagnosis is reported. Prenatal diagnosis was verified after termination of pregnancy. Molecular analysis by multiplex ligation-dependent probe amplification revealed a COL1А2 deletion in exon 50.

Introduction. Hypertrophic cardiomyopathy is one of the most frequent monogenic cardiovascular diseases. However, diagnosis of primary HCM is very challenging due to many causes of secondary hypertrophy. Genetic causes of HCM are also quite diverse - after screening of all causative genes known, mutations can be identified in 60% of familial cases. The aim of this study was to investigate mutation spectrum of MYBPC3 gene in the group of patients with myocardium hypertrophy. Material and methods. DNA samples of 77 patients with myocardium hypertrophy were collected. Mutation screening was performed by Sander sequencing of MYBPC3 gene or by semiconductor sequencing of MYBPC3 gene as a part of gene panel on Ion Torrent platform followed by confirmation of detected variants by Sanger sequencing. Results and discussion. In MYBPC3 gene 6 mutations were detected in 10 unrelated families. Also 4 variants of unknown clinical significance were found and 2 frequent coding polymorphisms. Nonsense mutation p.Q1233* was found in 5 unrelated families (6.5% of cases). Conclusion. Mutations in MYBPC3 gene were detected in 10 unrelated probands. Relatively low frequency of MYBPC3 mutations can be due to clinical heterogeneity of myocardium hypertrophy. Nevertheless, screening of gene panels is appears to be more promising in HCM patients, than partial sequencing of genes involved.

HDSL is a rare late-onset dominant disorder produced by CSF1R mutations. Rapidly progressing frontal lobe dementia is a main feature. First Russian case in 41-yеar-old female diagnosed by targeted NGS is an example of method value.

The paper presents a case report of muscular dystrophy manifested in the 5-year-old patient in muscles weakness of the upper and lower extremities. The Becker muscular dystrophy was diagnosed on the basis of clinical symptoms, electromyogram data, activity of creatine phosphokinase and «mild form» of dystrophy. The cardiac abnormalities manifested in age of 40 years in irregular heart rhythm and conduction disease, ventricular dilatation and left ventricular systolic dysfunction indicated lamin-associated genesis of Emery-Dreifuss muscular dystrophy (EDMD). Analysis of lamin A/C gene ( LMNA ) revealed heterozygous mutation с.1247С>G ( Thr528Arg , rs57629361, NM_001257374.2) in exon 9. The mutation was not found in first-degree relatives. The study of pedigrees showed that EDMD has not been characterized for the patient’s family previously, as well as other types of muscular dystrophy.

Genome editing technologies, including the newly appeared CRISPR/Cas9, are the most promising for development of etiotropic treatment of cystic fibrosis. Traditional transfection methods are commonly used to deliver components of CRISPR/Cas9 system. We aimed at optimizing non-viral delivery of plasmid pEGFP-N1 into human tracheal epithelial cells CFTE29o^- with homozygous F508del mutation. Efficiency of lipofection with various reagents, Metafectene, Metafectene Pro, Unifectine-56 and Maxifectine-56, was very low and poorly reproducible. Electroporation, even in «soft» conditions, led to high cell mortality. Calcium phosphate transfection turned out to be suitable for CFTE29o^- showing efficiency of 46.3-48.0%. High efficacy of this method allows to transfect CRISPR/Cas9 plasmids for their further comparative characterization in order to optimize genome editing of F508del mutation in CFTR gene.

There was considered the case of a rare hereditary disease of LEOPARD syndrome among representatives of four generations of the family. The diagnosis was exhibited on a set of clinical and phenotypic characteristics, confirmed by molecular genetic methods.

Williams-Beuren syndrome (WBS) is a multisystem genomic disorder, caused by deletion on chromosome region 7q11.23. Majority of cases occur sporadically, and a few familial cases have been described. We report on the first case of WBS in three relatives in three generations with maternally transmission of the microdeletion. Intrafamilial variability of the clinical features was shown.

Genotyping of STAT4 gene rs7574865 and CTLA4 gene rs5742909 variants hasn’t shown any statistically significant differences in the allele and genotype frequency distribution when comparing groups of JIA patients (n = 80) and controls (n = 80). However, after stratification by JIA subtype the T allele of rs7574865 variant of STAT4 gene was associated with polyarticular JIA. To clarify the exact role of the polymorphisms studied in predisposition to JIA, extension of investigated groups sample size is required.