Common Variants in the TYR Gene with Unclear Pathogenicity as the Cause of Oculocutaneous Albinism in a Cohort of Russian Patients

• Published in: Biomedicines 2024-10, Vol.12 (10), p.2234
• Main Authors: Shchagina, Olga, Stepanova, Anna, Mishakova, Polina, Kadyshev, Vitaliy, Demina, Nina, Bessonova, Ludmila, Ionova, Sofya, Guseva, Daria, Marakhonov, Andrey, Zinchenko, Rena, Kutsev, Sergey, Polyakov, Aleksander
• Format: Article
• Language: English
• Subjects: Albinism; Alleles; Gene frequency; Genes; Haplotypes; hypomorphic variants; Mutation; oculocutaneous albinism; Pathogenicity; Patients; Pigmentation; Population genetics; Statistical analysis; TYR; TYR gene
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12102234

oculocutaneous albinism (OCA) is a hereditary impairment of skin, hair, and eye pigmentation. The most common form of albinism is autosomal recessive albinism, caused by mutations in the gene, accounting for approximately 40-50% of all cases of the disease in European populations. Common hypomorphic variants in the gene could lead to a mild form of albinism in a compound heterozygous state with a pathogenic variant. : we examined by allele specific MLPA a cohort consisting of 118 unrelated patients with albinism and 10 parents of these patients. The control cohort consisted of 200 unexamined Russian residents. : the patients with albinism were divided into three groups: without pathogenic variants in the gene-70 patients, with one pathogenic variant in the gene-20 patients, and with two pathogenic variants in the gene-28 patients. Among the 20 patients with a single heterozygous variant in the gene, 15 patients had the c.575C>A p.(Ser192Tyr) variant, and 15 had the c.1205G>A p.(Arg402Gln) variant. Both the c.575C>A p.(Ser192Tyr) and c.1205G>A p.(Arg402Gln) variants were identified in 12 patients. In addition to the aforementioned variants, an intronic variant c.1185-6208A>G (rs147546939) was identified in seven patients. : the frequencies and the number of alleles c.575A, c.1205A, and c.1185-6208G in different groups of patients and the control group were compared. In this study, we demonstrate that the complex alleles [c.575C>A p.(Ser192Tyr); c.1205G>A p.(Arg402Gln)] and [c.575C>A p.(Ser192Tyr); c.1185-6208A>G; c.1205G>A p.(Arg402Gln)] are associated with oculocutaneous albinism, which is consistent with findings from other researchers.