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Information × Registration Number 0225U004879, (0121U110054) , R & D reports Title Molecular-genetic mechanisms of human disorders of sexual development popup.stage_title Повноекзомне секвенування в групі пацієнтів з ПРДС, аналіз .vcf файлів, вирівнювання відносно референсної збірки, фільтрування виявлених варіантів поліморфізму мононуклеотидних замін та мутацій типу indel, аналіз консервативності локуса та сегрегаційний аналіз для виявлення функціонально значущих варіантів патогенності мутації. Контроль виявлених мутантних варіантів шляхом секвенування за Сенгером продуктів ПЛР, отриманих гна базі ДНК матриці до складу якої входить досліджувані мутантні варіанти. Head Livshyts Liudmyla A., д.б.н. Registration Date 22-12-2025 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description1 Identify pathogenic mutations in determinant genes, disorders of which lead to diseases associated with impaired development of sex differentiation. Identify new candidate genes in which mutations are associated with impaired sex differentiation. Develop new effective information tools for the analysis of full-genome sequencing data to effectively assess the pathogenicity of identified genetic variants as a basis for genetic diagnosis and personalized therapy. popup.description2 Results. During the study, the nature and origin of new genetic variants (mutations) in known determinant genes leading to impaired development and differentiation of the genital organs were determined. According to the plan, a clinical and genealogical analysis was conducted among patients with impaired development and differentiation of sex from different regions of Ukraine, included in the study according to informed consent. Peripheral blood samples were obtained from patients and their family members (parents and, if available, other relatives) and genomic DNA preparations and, if necessary, mRNA were isolated and purified with subsequent cDNA synthesis. Subsequently, molecular cytogenetic analysis of patients was performed. In patients without chromosomal aberrations and mutations in genes included in the specific panel of genetic factors of disorders of sex development (AR, SRY, NR5A1, DMRT1) as well as in the parents of patients, whole-exome sequencing was performed. Validation of annotated mutant variants detected by whole-exome sequencing was performed by Sanger sequencing. In a patient with 46XY, SRY+ and a diagnosis of gonadal dysgenesis (full form), a missense mutation in the GATA4 gene c.34G>C (p.Gly12Arg) was first identified. Based on the results of in silico modeling of the protein with this mutation, possible molecular mechanisms of the pathogenesis of sexual development disorders were established. The phenomenon of incomplete penetrance of mutations in the GATA4 gene was also revealed. Product Description popup.authors Gorodna Oleksandra V. Kryl Nataliya M. Maryna V. Nechyporenko Hanna B. Livshyts Sirokha Dmytro А. Oleksandr S. Tarakanov popup.nrat_date 2025-12-22 Close