A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism

Abstract

Background: The purpose of this study was to elucidate the molecular basis of ocular albinism type I in a Chinese pedigree.

Methodology/principal findings: Complete ophthalmologic examinations were performed on 4 patients, 7 carriers and 17 unaffected individuals in this five-generation family. All coding exons of four-point-one (4.1), ezrin, radixin, moesin (FERM) domain-containing 7 (FRMD7) and G protein-coupled receptor 143 (GPR143) genes were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Ocular albinism and nystagmus were found in all patients of this family. Macular hypoplasia was present in the patients including the proband. A novel nonsense hemizygous mutation c.807T>A in the GPR143 gene was identified in four patients and the heterozygous mutation was found in seven asymptomatic individuals. This mutation is a substitution of tyrosine for adenine which leads to a premature stop codon at position 269 (p.Y269X) of GPR143.

Conclusions/significance: This is the first report that p.Y269X mutation of GPR143 gene is responsible for the pathogenesis of familial ocular albinism. These results expand the mutation spectrum of GPR143, and demonstrate the clinical characteristics of ocular albinism type I in Chinese population.

Figure 1. The pedigree of X-linked OA1.

A filled square indicates an affected male and a dot in the middle of the circle indicates a carrier. The proband is marked by an arrow. The underline indicates family members enrolled in this study.

Figure 2. Fundus photographs of three patients, one carrier and one normal individual.

A–F: three patients; G–H: one carrier; I–J: one normal individual.

Figure 3. OCT test photographs of three patients, one carrier and one normal individual.

A–F: three patients; G–H: one carrier; I–J: one normal individual. It should be noted that detailed structural imaging of the fovea was not successfully obtained in two patients (III:19 and III:30) with more severe nystagmus due to their poor fixation. Foveal image of one patient (IV:19) with relatively mild nystagmus was obtained.