Genetic analysis of albinism caused by compound heterozygous mutation of OCA2 gene in a Chinese family

Abstract

Background Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic oculocutaneous albinism (OCA) in a Chinese Han family. Methods We conducted a comprehensive clinical examination of the family members, screened the mutation gene sites using the whole exon sequencing (WES) technology, and verified the sites with Sanger sequencing. Results The clinical manifestations of the patient were white skin, yellow hair, freckles in the area of exposure, decreased vision, blue iris, the central fovea of the macula being underdeveloped, and the pigmentation of the fundus being insufficient. The WES test results indicate that the patient has a compound heterozygous mutation in the OCA2 gene (c.1258G>A (p.G420R), c.1441G>A (p.A481T), and c.2267-2A>C), respectively, originating from her parents. Among them, c.1258G>A (p.G420R) is a novel variant with extremely high pathogenicity. Our analysis suggests that the compound heterozygous mutation in the OCA2 gene may be the main cause of morbidity in this patient. Conclusions The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G>A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.