Exome sequencing analysis identifies novel homozygous mutation in in a Chinese family with Stargardt disease.

Aim: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations.

Methods: A Chinese STGD family and 200 normal controls were collected. Whole exome sequencing (WES) and bioinformatics analysis were performed to find the pathogenic gene mutation. Physico-chemical parameters of mutant and wildtype proteins were computed by ProtParam tool. Domains analysis was performed by SMART online software. HOPE online software was used to analyze the structural effects of mutation. Immunofluorescence, quantitative real-time polymerase chain reaction and Western blotting were used for expression analysis.

Results: Using WES, a novel homozygous mutation (NM_000350: c.G3190C, p.G1064R) in gene was identified. This mutation showed co-segregation with phenotype in this family. It was not found in the 200 unrelated health controls and absent from any databases. It was considered "Deleterious" as predicted by five function prediction softwares, and was highly conserved during evolution. was expressed highly in the human eye and mouse retina. The p.G1064R was located in AAA domain, may force the local backbone into an incorrect conformation, disturb the local structure, and reduce the activity of ATPase resulting in the disease pathology.

Conclusion: We define a novel pathogenic mutation (c.G3190C of ) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations.