Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

Abstract

BackgroundAutosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolic profile of a consanguineous Chinese family with ARB.MethodsOphthalmic examinations were performed on affected patients with ARB. Target capture sequencing was performed to screen causative mutations in 256 known retinal disease genes and Sanger sequencing were used for verification. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature.ResultsAffected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in BEST1 gene (chr11:61725867G>A) of the proband. Sanger sequencing further confirmed the mutation. The blood metabolic profiles were highly similar among all family members probably due to the same life style, habitats and genomic background. However, ARB patients presented significant deregulation of metabolites such as Citric acid, L-Threonic acid, Eicosapentaenoic acid.Conclusions We identified a novel disease-associated variant in BEST1 gene as well as a disease-specific metabolic feature in familial ARB. The findings improved the understanding of mechanisms of ARB and provided a potential therapeutic strategy with application of metabolomics.