Identification of a novel GPR143 mutation in X-linked ocular albinism with marked intrafamilial phenotypic variability

Ocular albinism type 1 (OA1) is an X-linked inherited disease characterized by impaired visual acuity, congenital nystagmus, foveal hypoplasia, hypopigmentation of iris and fundus. It is caused by mutations in the G protein-coupled receptor 143 (GPR143) gene. The genetic characteristics of OA1 have not been well defined in Asians. In this study, six members from three consecutive generations of a Korean family with OA1 were enrolled. We performed whole-exome sequencing followed by validation and segregation analysis. Two affected patients underwent detailed ophthalmic examinations and eye movement recordings. Of the two affected males, the proband had all classical phenotypes of OA1, but the other showed isolated foveal hypoplasia without nystagmus. We identified a hemizygous missense (c.623C>A, p.Ala208Glu) mutation of GPR143 in affected males. This mutation was also present as heterozygous in two obligate female carriers, and was not found in unaffected members. Our data expands the spectrum of phenotypes and genotype in GPR143 in Asians, and highlights the phenotypic heterogeneity in OA1.