Introduction. TRPV4 -associated skeletal dysplasias are a genetically heterogeneous group of autosomal dominant disorders caused by mutations in the TRPV4 gene. TRPV4 contains 16 exons and encodes a Ca2+-permeable transmembrane channel protein. To date, seven nosological forms within this group of skeletal dysplasias have been described. The overall prevalence of these disorders does not exceed 1:1,000,000. The most frequent forms among this group are spondylometaphyseal dysplasia, Kozlowski type (OMIM:184252) and metatropic dysplasia (OMIM:156530). Objective: to describe the clinical and genetic characteristics of Russian patients with skeletal dysplasia caused by previously reported and newly identified mutations in the TRPV4 gene. Methods. A comprehensive examination of 15 children from unrelated families aged 10 days-15 years with clinical and radiological signs of TRPV4-associated skeletal dysplasia was carried out. To specify diagnosis we used genealogical analysis, clinical examination, neurological examination according to a standard method with an assessment of the psycho-emotional sphere, radiography and sequencing a targeted gene panel including 166 genes responsible for the development of hereditary skeletal disorders. Results. Spondylometaphyseal dysplasia, Kozlowski type was diagnosed in 7 and metatropic dysplasia in 8 patients. 7 pathogenic variants in the TRPV4 gene were identified, of which two were novel. As in previously reported cases, two major mutations in the TRPV4 gene were found in Russian patients: p.Arg594His in patients with spondylometaphyseal dysplasia, Kozlowski type and p.Pro799Leu in patients with metatropic dysplasia. Conclusion. Our findings combined with previously reported results suggest the rationale for creating a genetic screening test to detect major mutations in patients with spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia, which have similar clinical and radiological manifestations. Foremost use of this test will improve the molecular diagnostics of these diseases.

A search was made for associations of polymorphic thrombophilia gene loci with infertility and different ovarian responses to ovulation stimulation. Based on obstetric anamnesis data, 280 women were differentiated into three groups depending on the presence of a reproductive disorder: group 1 - women with infertility (n=83); Group 2 - women with habitual miscarriage (т=79). The comparison group included women with multiple term deliveries without a hereditary tendency to form blood clots (n=118). The study was conducted using real-time polymerase chain reaction. Statistical analysis was performed using the Kruskell-Wallace criteria, median test, Pearson’s χ2 test, using the Statistica 12 software package. The association of the G allele of the rs1799963 locus of the F2 gene, the G allele and the GG genotype of the rs6025 locus of the F5 gene with infertility was revealed. Associations of the G allele and the *GG genotype of the rs6046 locus of the F7 gene with a poor response to ovulation stimulation, as well as with ovarian hyperresponse, were found.

We presented a clinical case report about the complexity of the choice of pregnancy management when identifying the X-chromosome duplication using prenatal diagnostic methods. Thus, a chromosomal rearrangement dup(X)(q13.3q21.1) was diagnosed by molecular karyotyping of amniotic fluid in a female fetus with phenotype features: left hand polydactyly, right hand polydactyly in question, hyperechoic intestine.

Mitochondrial diseases are clinically and genetically heterogeneous group of inherited diseases resulting from impaired oxidative phosphorylation in mitochondria. One of the most common representatives of this group among children is Leigh syndrome, or subacute necrotizing encephalomyelopathy, a severe neurodegenerative disease with manifestation in childhood. The characteristic neuroradiological features are bilateral symmetrical hypointensities in the basal ganglia on CT or bilateral symmetrical hyperintense lesions in the brainstem and/or basal ganglia on T2-weighted MRI. Currently, 80 genes are known that are responsible for the development of LS, which significantly complicates the diagnosis. In the review we provide clinical and molecular genetic features, current approaches in diagnostic and treatment for LS. Finally, an algorithm for the complex diagnosis of LS including regional aspects of mutational spectrum is described.

Information obtained from genetic testing is considered as a part of health information, but it has a special status due to its predictive nature, the ability to detect DNA sequence variants that are relevant to human health in the future, but not related to the original purpose of testing, potential changes in interpretation test results as scientific knowledge accumulates, as well as with a family character. Due to the complexity of interpreting genetic information and the potential medical, psychological, and social implications associated with genetic testing, informed consent is required from patients or their legal representatives, as well as genetic counseling before and after testing. The review discusses the features of genetic information and the corresponding features of informed consent in genetic and genomic testing, storage of genetic information and biosamples, and newborn screening.