Aim. The aim of the study was to investigated whether polymorphisms С677Т and А1298С of the MTHFR gene are associated with neural tube defects (NTDs) in the Kyrgyz population. Methods. The study included 76 children and their mothers. The study group included 30 children and their mothers, where the child had a neural tube defect, most commonly in the form of an isolated spina bifida or in combination with congenital anomalies. Control group - 46 children without congenital malformations. С677Т and А1298С polymorphisms analysis in the MTHFR gene were performed by PCR-RFLP method. Results. The frequency of the heterozygous A1298C genotype (χ²=9,67; p=0,0079) and 1298C allele (χ²=4,10; p=0,041) of the MTHFR gene was higher in cases than in controls. Child with heterozygous A1298C genotype had a 4,71- fold (OR=4,71; p=0,0079) higher risk of NTDs when compared with those who had the AA genotype. Child carriers of the 1298C allele had a 2,2-fold higher risk of NTDs (OR=2,20; p=0,041). С677Т/А1298С genotypes are more frequent among cases than controls (χ²=5,00; p=0,025). We showed that the combinations of С677Т/А1298С is strong association with NTDs (χ²=5,60; p=0,018). Subjects carriers of the combinations of С677Т/А1298С genotypes had a significant 9,7-fold higher risk of NTDs (OR=9,75; p=0,018). Conclusion. There is significant association between С677Т and А1298С polymorphism in MTHFR gene and neural tube defects in the Kyrgyz population. An increased risk of neural tube defects associated with heterozygous A1298C genotype, 1298C allele and combinations of С677Т/А1298С in MTHFR gene.

In this article we continue to describe the pathogenic variants of the CFTR gene identified among Russian cystic fibrosis (CF) patients. For the first time the clinical and genetic characteristics of the mutation c.1083G> A (p.Trp361 *) are presented. The pathogenic genetic variant c.1083G> A (p.Trp361 *) of the CFTR gene belongs to the nonsense mutations (class I) and was listed for the first time in the CFTR1 database (http://www.genet.sickkids.on.ca) by Professor Milan Macek et al. in mid-2019 without any description of clinical manifestations of cystic fibrosis. Methods. The data of the National Register of Patients with Cystic Fibrosis of the Russian Federation 2017 were analyzed. Outpatient records and case histories of two patients from unrelated families carrying a rare genetic variant c.1083G> A (p.Trp361 *) were analyzed. To determine the Intestinal current measurement (ICM) and Forskolin-induced swelling (FIS) in intestinal organoids, rectal biopsy material of CF patients was used. DNA for sequencing was isolated from leukocytes of venous blood of the patients. Results. Variant c.1083G> A (p.Trp361 *) was found in two patients from unrelated families from different regions of the Russian Federation, according to the Register of Cystic Fibrosis Patients in the Russian Federation 2017. Analysis of clinical manifestations of the disease in children 6 and 9 years old showed the presence of chronic pancreatic insufficiency, more expressed in one child with a history of distal intestinal obstruction syndrome. The clinical manifestation of the second patient was characterized by the development of transient hyperbilirubinemia, Pseudo-Bartter’s syndrome at an early age, and subsequently repeated episodes of bronchial obstruction and the development of polypoid rhinosinusitis. The ICM method and the FIS in intestinal organoids showed that the genetic variant c.1083G> A (p.Trp361 *) refers to the variants of the CFTR gene with the absence of chlorine channel function. Conclusion. The clinical picture of cystic fibrosis in two patients from unrelated families with the pathogenic variant c.1083G> A (p.Trp361 *) in the compound with variant c.1521_1523delCTT (p.Phe508del) (variant legacy name F508del) and results of the evaluation of the CFTR protein functions, obtained by the method of ICM and using the FIS assay in intestinal organoids, are presented for the first time. Patients continue to be under the control in Russian CF centers.

Purpose: the study aim was to determine and analyze woman’s attitude to carrier screening of the most common autosomal recessive diseases. Methods. For the study, a questionnaire was developed containing 11 questions to assess the attitude of women to various types of diagnostics. The survey involved 244 women of reproducrive age from 18 till 50 years. Results. 81.1% of respondents expressed a desire to undergo carrier screening before conception. 64.3% would support their partner when partner’s carrier status established and consulted with doctor together. 60.7% of respondents would like to undergo prenatal diagnostic after establishing the status of carriage in both partners. Conclusion. In general, women reacted positively to the possibility of passing carrier screening. It was also noted that the results of the screening will have low effect on the married couples.

Background and objectives. High incidence and high prevalence of hereditary diseases in Yakut ethnic group of Republic of Sakha (Yakutia) has been reported by several research groups. The incidence of some of the diseases are much higher comparing to data in other regions of Russia and the worldwide. There is a pressing need for prevention of those diseases through the mass genetic screening of population. The methods of genetic diagnostics that are known today are not able to afford the mass screening due to the high cost and time consumption for a single test. One of promising technologies and methods of DNA diagnostics is DNA microarray. It enables researchers to quickly screen large numbers of biological analytes for a variety of purposes including disease diagnostics. Methods. A Perkin Elmer Piezzorray (Perkin Elmer) microarrayer was used to print oligonucleotide based low-density microarrays by non-contact manner for addressing 5 mutations causing 5 frequently occurring diseases reported from yakut population. The assay using developed microarray chip based on reverse hybridization which include two step multiplex PCR reactions with production of one-stranded Cy5 labeled-PCR products following its hybridization with oligonucleotide probes. Results. In this study we developed a DNA microarray for detection of mutations in genes CUL7, NBAS, FAH, DIA1, GJB2 genes which are known to be cause of five very frequently occurring hereditary diseases in republic of Sakha (Yakutia): 3-M syndrome, SOPH-syndrome, tyrosinemia type 1, methaemoglobinaemia type 1, nonsyndromic hearing loss and deafness (DFNB1) type 1A respectively. Testing of experimental versions of DNA chips as well as control DNA diagnostic of five hereditary diseases on the same DNA samples using PCR with PCR and restriction enzyme analysis and real-time PCR were carried out.

We report on a case of Emanuel syndrome on a newborn girl with congenital heart defect and high bowel obstruction, karyotype: 47,XX,+der(22)t(11;22)(q11.2;q23)pat. The report contains brief review of information from literature about formation of such rearrangement, clinical implications, and genetic counseling for this syndrome.

Ring chromosome 3 is a rare chromosomal abnormality with a highly variable phenotype principally characterized by pre- and postnatal growth retardation, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features. The presence of a ring chromosome causes mitotic instability and often results in dynamic mosaicism with cells showing chromosomal or segmental aneuploidies and leading to various phenotypic consequences. We present a case of mitotic instability of ring chromosome 3 in a child with multiple malformations and developmental abnormalities. Aim: The investigation of ring chromosome 3 instability at mitosis. Methods: FISH with DNA probe on chromosome 3. Results: The karyotype of a child - 46,XX,r(3)(p26q29). FISH analysis revealed a mosaic clones derived from ring chromosome 3. Conclusions: The ring chromosomes are unstable at mitosis and lead to the formation of somatic dynamic mosaicism. Mitotic instability of ring chromosome 3 demonstrates the influence of secondary genetic imbalance on severity of symptoms in our patient.