Wilson’s disease is a genetic, autosomal recessive disorder in which excessive amount of copper accumulates in the liver, brain, kidneys and cornea, causing hepatic and neurological abnormalities. The incidence of the disease is approximately 1 in 30,000 worldwide. WD is associated with ATP7B gene, which codes a copper - transporting ATPase. This review summarizes the molecular genetics reasons and biochemical characteristics, genotype-phenotype correlations and gender differences in Wilson’s disease.

The diversity of monogenic hereditary diseases in Karachays of 10 rural districts and two cities of the Karachay-Cherkess Republic was estimated. The surveyed population size was 382630 people (162444 Karachays). 142 nosological forms were revealed, including 75 diseases with autosomal dominant (AD, 428 patients from 250 families), 50 diseases with autosomal recessive (AR, 341 patients out of 289 families), and 17 conditions with the X-linked mode of inheritance (75 affected from 57 families). In total, 844 patients from 596 families were registered. The frequency of hereditary disorders appeared to be 1:192 Karachays. A comparative analysis of the diversity of AD and AR hereditary diseases was performed with the previously studied populations / ethnic groups of the European part of Russia: Kirov, Kostroma, Tver, Bryansk, Rostov regions, Krasnodar Krai, Republics of Adygea, Tatarstan, Bashkortostan, Mari El, Udmurtia, and Chuvashia.

Clinical cases of rare inborn neurometabolic diseases associated with tetrahydrobiopterin metabolic disorders are given. Such diseases are usually detected by mass neonatal screening for phenylketonuria, some of them are characterized by hyperphenylalaninemia. Effective treatment methods were developed for such diseases, diagnostic protocols for hyperphenylalaninemia were revised. We studied biopterin profile in blood and urine of 49 patients with hyperphenylalaninemia, and in 3 patients with tetrahydropterin-deficient syndrome. Clinical features and diagnostics were described.

Purpose. The purpose of this work was to describe the clinical and genetic characteristics of the patient with Nicolaides-Baraitser syndrome, caused by the previously not described missense mutation in the SMARCA2 gene. Materials and methods. Video EEG monitoring was carried out in accordance with the international system 10-20 s. Cup electrodes, which were fixed with the help of colloidal glue, were used. Exom sequencing was carried out on an Illumina NextSeq 500 sequencer with an average coverage of at least 70-100x using a panel containing 211 genes. The pathogenicity of the detected mutation was confirmed by Senger sequencing using the DNA of the patient and his parents. Results. In the patient we observed with a previously unidentified single nucleotide substitution in the gene in the 7 exon of the SMARCA2 gene, the main clinical manifestations were characterized by a combination of moderate mental retardation, a violation of expressive speech, and not pronounced dysmorphic features of the facial features characteristic of the Nicolaides-Baraitser syndrome. However, the patient described by us did not have some phenotypic signs. A sufficiently mild phenotype can be explained by the small significance of the small helicase domain encoded by the 7 exon gene in which the nucleotide replacement occurred, for the functioning of the protein. Conclusions. Taking into account all the above, it can be concluded that the variability of the clinical picture of hereditary diseases is due to the localization of the pathogenic mutation in the gene and the functional significance of the domain whose activity it violates. Thus, the description of new clinical cases of rare syndromes caused by previously not described mutations is of great importance not only for the practicing geneticist, but also for the development of molecular genetics in general and a deeper understanding of genotype-phenotype correlations.

Massive parallel sequencing (MPS) are the most progress and success of technologies in genetic researches. However, the new technologies bring challenges in terms of data management, as well as for the bioinformatics and interpretation of result. This guideline for the evaluation and validation of MPS data is the first document in Russian Federation. A group of bioinformatics, laboratory genetics and clinical genetics worked at these guidelines. We believe that these recommendations would help to stakeholders in the field of human genetics uniforming and managing MPS data.