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. 2024 Oct 1;12(10):2234.
doi: 10.3390/biomedicines12102234.

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

Olga Shchagina  1 , Anna Stepanova  1 , Polina Mishakova  1 , Vitaliy Kadyshev  1 , Nina Demina  1 , Ludmila Bessonova  1 , Sofya Ionova  1 , Daria Guseva  1 , Andrey Marakhonov  1 , Rena Zinchenko  1 , Sergey Kutsev  1 , Aleksander Polyakov  1
Affiliations

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

Olga Shchagina et al. Biomedicines. .

Abstract

Background: 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 TYR gene, accounting for approximately 40-50% of all cases of the disease in European populations. Common hypomorphic variants in the TYR gene could lead to a mild form of albinism in a compound heterozygous state with a pathogenic variant. Methods: 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. Results: the patients with albinism were divided into three groups: without pathogenic variants in the TYR gene-70 patients, with one pathogenic variant in the TYR gene-20 patients, and with two pathogenic variants in the TYR gene-28 patients. Among the 20 patients with a single heterozygous variant in the TYR 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. Conclusions: 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.

Keywords: TYR; hypomorphic variants; oculocutaneous albinism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Results of visualization for the c.575C>A p.(Ser192Tyr), c.1205G>A p.(Arg402Gln), and c.1185-6208A>G variants. λ/PST1—molecular weight marker—phage’s λ DNA treated with PST1 restriction endonuclease, Lines 1–9—results of MLPA analysis for samples with different genotypes, NC—negative control.
Figure 2
Figure 2
Accumulation number of alleles c.575A, c.1185-6208G, and c.1205A in the studied groups.
See this image and copyright information in PMC

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