Muscular dystrophies are the group of hereditary neuromuscular disorders characterized by progressive musclular weakness and degeneration of muscles. The most common of them are Duchenne muscular dystrophy (DMD) and Landouzi-Dejerine facioscapulohumeral muscular dystrophy (FSHD). To date, the pathogenesis of these diseases is well studied that allow to develop various therapeutic approaches for the treatment. Several drugs for the Duchenne muscular dystrophy get through all stages of clinical trials approved by FDA (food drug administration) and are utilized for treatment. Pathogenesis of FSHD differs substantially from DMD, and therapeutic approaches are only under development. Molecular and cellular technologies as well as the understanding of the disease pathogenesis allow to hope for a quick success in this area.

Associations of the first phase xenobiotic biotransformation system genes with the severity of cystic fibrosis (CF), adverse side effects and antibiotic resistance to intravenious antibiotic therapy in CF children were studied in the presented survey. The number of examined CF children amounted to 118, healthy sample of 70 individuals. All surveyed children reside in the European part of Russia. Study of 6 polymorphisms in 4 genes of the first phase biotransformation system of xenobiotics, CYP2C9, CYP2C19, CYP2D6, CYP3A4 was carried out by RFLP analysis. There were no significant differences in the frequency of alleles and genotypes of the studied polymorphisms between the groups of healthy and children with CF, excluding the higher allele frequency of CYP2D6*4 in the total group of MV patients (p = 0,023), as well as between groups of CF patients that have the resistant to antibiotic therapy microflora of the respiratory tract, and not having such, and in groups of patients receiving 3 or more course of intravenous therapy for a year and receiving antibiotic therapy at least 2 times during the year. There is a tendency to increase the frequencies of CYP2C9*3 allele and heterozygous CYP2C9*3/CYP2C9*1 genotype in the group of children receiving intravenous antibiotic therapy sporadically or not receiving at all compared to receiving intravenous antibiotic therapy for more than 3 times a year (p<0,1). Association of CYP3A4*1B allele and CYP3A4*1B/*1A genotype with the adverse side effects to antibacterial drugs was identified (p = 0.023 and p = 0,025). The carrier state of the heterozygous genotype CYP3A4*1B/*1A and the carrier state of the CYP3A4*1B/*1A(-392C/T) Ч CYP2D6*1/*1(1846G/G) combined genotype can be regarded as markers for increased risk of adverse response to intravenous antibiotic therapy in CF patients (OR = 8,50 (95%CI of 1.64-44,04) and OR = 35,00 (95%CI 3,29-372,14), respectively).

Congenital cataracts are a major cause of vision loss in children worldwide. Congenital autosomal recessive cataract is one of the most common orphan diseases in indigenous Yakut population (the Sakha Republic, Eastern Siberia, Russia). To identify the genetic cause of congenital cataract spread in Yakut population we performed whole exome sequencing on Illumina NextSeq 500 in one Yakut patient from family with three affected siblings, whose parents had preserved vision and revealed novel homozygous transition c.1621C>T (chr3:46009205G>A) in gene FYCO1 (3p21.31) previously known in association with congenital cataract. The c.1621C>T transition leads to premature stop-codon formation (p.Gln541*, NM_024513.3) in exon 8 of the FYCO1 gene. Variant c.1621C>T is not reported in the 1000 Genomes, the ESP6500, and the ExAC projects. Sanger sequencing confirmed the segregation of homozygosity for c.1621C>T with congenital cataract in this Yakut family: all affected siblings were homozygotes for c.1621C>T while their healthy parents were heterozygous for this variant. Subsequent screening c.1621C>T in other patients with congenital cataract allowed us to define the contribution of c.1621C>T in etiology of this disease in Yakutia. In total, 87.5% of the congenital cataract cases in Yakutia were caused by homozygous variant c.1621C>T (p.Gln541*) in the FYCO1 gene. The highest prevalence of congenital cataract caused by homozygosity for c.1621C>T was registered in the сentral districts of the Sakha Republic (Yakutia). These results suggest that the novel transition c.1621C>T (p.Gln541*) in the FYCO1 gene is a major cause of congenital autosomal recessive cataract (CTRCT18) in Yakut population in the Sakha Republic (Yakutia).

Chromosomal abnormalities are a common cause of miscarriage, or if karyotype changes are compatible with life, the birth of children with severe developmental disabilities. Cytogenetic analysis in miscarriages makes it possible to establish the cause of pregnancy loss and to conduct an objective counseling of the couple. At the present time to detect abnormalities of the karyotype, along with the standard metaphase analysis methods comparative genomic hybridization, interphase FISH-analysis, quantitative fluorescent PCR and MLPA are used. The advantage of methods based on fluorescence quantitative PCR is their speed, efficiency and lack of strict requirements for the test material. The results of DNA diagnostics in 1239 embryos who died in utero, using new medical technology which is an effective method of rapid quantitative detection of abnormalities of genetic material by amplification of highly polymorphic microsatellite DNA loci with fluorescently labeled oligonucleotide primers. The diagnostic panel includes eight chromosomes for which numerical abnormalities are most often found in the abortive material, as well as lead to the birth of children with severe developmental disabilities. In miscarried embryos chromosomal abnormalities were found in 418/1239 (34%) samples. The most common type of chromosomal abnormality was trisomy of the autosomes, the cumulative incidence of which amounted to 62.7% (262 samples) and full triploidy - 22% (93 samples). Among trisomies abnormalities of 16 and 22 chromosomes were predominant (64 cases and 102 respectively). Autosomal monosomies were rarely found, with the total rate of 4%. Chromosome X monosomy was detected in 28 (6.7%) cases. In 14 samples we identified combined trisomies of two autosomes.

Familial Mediterranean fever (FMF) is the most common autoinflammatory disease of Hereditary periodic fevers. FMF is characterized by attacks of periodic fever, aseptic peritonitis, abdominalgia, thoracalgia, arthritis, and other symptoms, typically lasting 2-3 days, once a month in average. FMF is monogenic disease with autosom-recessive type of inheritance in most cases. Although in populations with high frequency of FMF there is evidence of clinical manifestations among heterozygous patients. The aim of this study is to show our comparative data on FMF phenotypic manifestations among heterozygous and homozygous patients with the most common mutation in Armenian population.

The aim of this work is a definition of occurrence frequency distribution of BRCA1 and BRCA2 genes mutations between Tatar woman. By next generation sequencing (NGS) method we analyzed BRCA1 and BRCA2 genes in 56 blood samples from Tatar population patients with hereditary breast cancer (BC). 15 blood samples from patients with Slavic origin were taken as a comparison group. The analysis results show that between 56 Tatar origin patients with hereditary BC was identified 16 mutations in BRCA1/BRCA2 genes (28%). It was found significant difference in the presence of 5382insC mutation between Slavic and Tatar woman.