A novel mutation c.29G>A in the X-linked GPR143 gene causes ocular albinism type 1 in a family

This study conducted pathogenic gene mutation screening and analysis in a pedigree with ocular albinism type 1 (OA1). Affected individuals within the pedigree exhibited typical OA1 clinical features, including congenital bilateral visual impairment, nystagmus, strabismus, reduced iris and fundus pigmentation, and foveal hypoplasia. Whole-exome sequencing (WES) was performed on the proband, revealing a hemizygous mutation c.29G>A (p.Cys10Tyr) in the GPR143 gene located on the X chromosome. This mutation involves a guanine (G) to adenine (A) substitution at nucleotide position 29, resulting in the amino acid change cysteine (Cys) to tyrosine (Tyr) at position 10 of the encoded protein. Sanger sequencing confirmed the presence of this mutation in all affected family members. Bioinformatics analysis indicated that this mutation leads to alterations in the primary structure of the GPR143 protein, including increased molecular weight, isoelectric point (pI), and instability index. Changes in the secondary structure were also predicted, showing an increase in the proportion of alpha-helices and extended strands, accompanied by a decrease in the proportion of random coils. Multiple online prediction tools (PROVEAN, SIFT, Mutation Taster, and Polyphen-2) consistently classified this mutation as pathogenic. This study identified and confirmed a novel pathogenic mutation, GPR143 c.29G>A, broadening the mutational spectrum of this gene. Furthermore, it provides new insights into the functional implications of the GPR143 protein from a protein conformational perspective.