Genetic Analysis of 28 Chinese Families With Tyrosinase-Positive Oculocutaneous Albinism

Abstract

Background: Tyrosinase-positive oculocutaneous albinism (OCA, type II, OCA2) is an autosomal recessive genetic disease in which the biosynthesis of melanin decreases in the skin, hair, and eyes. OCA2 disease is caused by mutations in OCA2 gene. The gene product plays a role in regulating the pH of melanosomes. Up to now, hundreds of OCA2 mutations have been reported and novel variants are still being discovered.

Methods: In this study, we reviewed the records of OCA2 patients who had conducted albinism genetic testing, and then analyzed the clinical and genetic information of 28 OCA2 patients who had been genetically diagnosed by using Sanger sequencing and next-generation sequencing.

Results: In this study, we reported 31 variants screened from 28 Chinese OCA2 families, and characterized the detailed molecular and clinical presentations. There were 12 novel variants among all detected variants, including 3 missense variants (p.G393V, p.T482A, and p.R720P), 4 frameshift variants (p.R53Gfs^∗49, p.N279Kfs^∗17, p.I469Lfs^∗4, p.I655Nfs^∗12), 2 splicing variants (c.1637-2A > G, c.1951 + 1G > C), 2 stopgain variants (p.L278X, p.W652X) and 1 insertion variants (p.P315LinsT). One potential cluster of missense variants was implicated indicating the important roles of the underlying domains in OCA2 pathogenesis.

Conclusion: Our results were beneficial for diagnosis and precision clinical management for OCA2-related disorder, and this study expanded the mutation spectrum of oculocutaneous albinism.

Keywords: OCA2 gene; missense variants; next-generation sequencing; novel variants; oculocutaneous albinism.

FIGURE 1

Variants pattern of OCA2. Loss-of-function variants are labeled above the diagram. Missense variants are labeled below the diagram. Purple region represents P-permease domain. * represents the novel variants.

FIGURE 2

Novel missense variants of OCA2. (A) Conservation analysis of OCA2 missense variants. (B) Simulation of the amino acids conformation changes by I-TASSER.