Heterogeneous group of hereditary spastic paraplegias includes by now about 80 forms with mapped and predominantly identified genes: SPG. Many of SPG were recognized recently by methods of next generation sequencing NGS. Aside from new SPG and their allelic variants discovering, NGS modifies knowledge about «old» forms, defines SPG epidemiology and suggests new ways of classifications.

Previously, by using whole exome sequencing (WES), the nonsense mutation c.1621C>T (p.Gln541*) in the FYCO1 gene was revealed as the main genetic cause of congenital autosomal recessive cataract causing of in the Sakha Republic. In this paper we present the results of the c.1621C>T (p.Gln541*) carrier frequency analysis in 424 adult individuals without of visual impairments from 7 populations of Eastern Siberia (Russians, Yakuts, Evenks, Evens, Dolgans, Yukaghirs, and Chukchi). The highest carrier frequency of mutation c.1621C>T (p.Gln541*) was found in Yakut population (7.9%), the lowest - in Evenks (1.7%) and Evens (2.0%), and c.1621C>T (p.Gln541*) was absent in Russians, Yukaghirs, Dolgans and Chukchi. The analysis of haplotypes obtained as a result of genotyping of 6 STR markers flanking the FYCO1 gene was carried out in 25 patients homozygous for mutation c.1621C>T (p.Gln541*) and in 114 patients without this mutation. Common haplotypes bearing c.1621C>T (p.Gln541*) indicate the role of founder effect in the spread of this mutation in Yakutia. The highest diversity of the c.1621C>T-haplotypes was revealed in ethno-territorial group of Central Yakuts inhabiting the Leno-Amginsky interfluve. The mutant haplotypes of the Vilyui and Northern Yakut groups are probably derived from the c.1621C>T-haplotypes found in the Central Yakuts. Our results suggest that the novel mutation c.1621C>T (p.Gln541*) in the FYCO1 gene causing of autosomal recessive cataract (CTRCT18) spread among Yakut isolate population in Eastern Siberia (Russia) as a result of founder effect about 260 ± 65 years ago (10.4 ± 2.6 generations) i.e. in the middle of the XVIII century.

The main laboratory test for the diagnosis of peroxisome diseases (PD) is the analysis of the concentration of very long chain fatty acids (VLCFA), their ratios, phytanic and pristanic acids in plasma. Until the beginning of 2017, only the detection of VLCFA and the analysis of several genes: ABCD1 , PEX1 , PEX6 were used to diagnose PD in the laboratory of inherited metabolic diseases (IMD). The purpose of the work was to expand the range of biochemical and DNA-tests to increase the effectiveness of diagnosis of PD. The analysis of the simultaneous determination of VLCFA, their ratios, phytanic and pristanic acids by gas chromatography-mass spectrometry (GC-MS) was tested, which allows to carry out confirmatory biochemical test. A target panel was developed that includes 15 genes of PEX, as well as genes responsible for X-ALD, Refsum’s disease and D-bifunctional protein deficiency for molecular genetic verification of the diagnosis. Using this approach, changes in the concentration of these metabolites were detected in 13 patients and the following diagnoses were verified on the basis of clinical data and the results of DNA diagnostics: D-bifunctional protein deficiency (n = 1), Zellweger syndrome (n = 1), X-linked adrenoleukodystrophy (n = 11). In 2 patients biochemical tests were used to confirm the pathogenicity of mutations detected during DNA diagnostics: Zellweger syndrome (n = 1), X-linked adrenoleukodystrophy (n = 1).

We performed a comprehensive molecular genetic examination of 76 patients with tuberous sclerosis. For establish molecular diagnosis of the disease, we applied a new medical technology that includes targeted high-throughput parallel DNA sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and Sanger sequencing. Search for point mutations and small indels in the TSC1 and TSC2 genes was carried out with next generation sequencing on the Ion S5 instrument. In order to filter out sequencing artifacts, to establish pathogenicity of the detected single nucleotide substitutions, and to identify familial cases, Sanger sequencing was performed. To search for extended deletions, the MLPA method was used. In 46% cases mutations have been detected, 70% in the TSC2 gene, and 30% in the TSC1 gene. Overwhelming majority of mutations were detected by NGS (91.9%), and 8.1% were detected by MLPA.

The aim of the study was to search for the association of the polymorphisms +936C/T and +460C/T of the VEGF gene and polymorphisms of C(-15161)T (rs10902088) and T(-12150)C (rs10794288) of the MUC2 gene with the risk of developing genital endometriosis in the Slavic population of the North-Western Federal District. The study included 60 patients (mean age 32.1 ± 12.4 years) with a diagnosis of external genital endometriosis and 76 healthy donors (mean age 29.6 ± 9.7 years). Genotyping was carried out by real-time PCR using the LightCycler 480 Instrument II (Roche, Switzerland) amplifiers and VEGF T(-460)C (rs833061), VEGF C936T (rs3025039), MUC2 C(-15161)T (rs10902088), MUC2 T(-12150)C (rs10794288) (Sintol). The association of C allele (OR = 2.11) and the СС genotype (OR = 2.57) of polymorphism rs833061460 in VEGFA gene with an increased risk of developing external genital endometriosis in Slavic population of the North-Western Federal District.

Introduction. Charcot-Marie-Tooth disease is clinical polymorphic and genetic heterogeneity group of peripheral nervous system disorders. Genetic counseling for CMT-families is a difficult problem for the doctor. Materials and methods. Autosomal dominant CMT-family from Samara was observed by сlinical, electrophysiological and molecular-genetic methods. Genetic research was performed by direct automatic sequencing of target genes and exome-sequencing on the IlluminaNextSeq 500 sequenator by method of pair and trailer reading (2kh75p.o) about use of the IlluminaTruSeq® ExomeKit set. Results. We identified a splice-site LRSAM1 gene mutation (c.2047-1G>A, p.Ala683ProfsX3). Today only 20 families with LRSAM1 mutations are described. The clinical features in this family is the late age of manifestation (on 4-5 decade of life), asymmetry of atrophy, the weak clinical manifestations and the slow. Conclusion. Genetic diagnostics for this CMT should be carried out by the NGS-methods. Genetic testing is the only way to determine the status of family members for the purpose of planning pre-conception prevention.

Adams-Oliver syndrome (AOS) - rare inherited disease, the main clinical characteristics are aplasia cutis congenital (ACC) of the scalp and terminal transverse limbs defects (TTLD). This syndrome is mostly inherited in autosomal dominant manner. The purpose of our work was to describe clinical and genetic characteristics of two patients who are appeared to be sibs in one family and both had rare autosomal dominant Adams-Oliver syndrome type 2 with new allelic variant in DOCK6 gene. In described case the proband has severe neurological symptoms as microcephaly, seizures, cerebral atrophy with hydrocephalus ex vacuo, spastic tetraparesis, and significant psychomotor retardation. However, distinct clinical symptoms were less pronounced, which is more pathognomonic to Adams-Oliver syndrome autosomal recessive type. Significant clinical intrafamilial polymorphism is detected in proband and his sister cases what is important to take into account in terms of genetic counseling.