BEST1 Variant Associated with an Atypical Macular and Peripheral Retinal Phenotype.

Abstract

Best vitelliform macular dystrophy (BVMD) is an inherited macular dystrophy associated with over 250 pathogenic variants of the Bestrophin-1 (BEST1) gene. While several of the types of lesions of BVMD are well-described, reports of phenotypic variations associated with rare genetic variants are limited. Retrospective case-series performed in 2021 at a tertiary eye care center. Three members of one family referred to a tertiary eye care clinic for evaluation of their autosomal dominant macular dystrophy. Study subjects presented with atypical findings of peripheral schisis-like lesions and atrophy with abnormal electroretinogram (ERG) in addition to typical macular lesions found in BVMD. Genetic analyses identified a heterozygous BEST1 c.227T>A, p.(Ile76Asn) pathogenic variant in all three subjects. This study represents the first report of the phenotype associated with the c.227T>A, p.(Ile76Asn) BEST1 variant, which - while mentioned twice in the literature - has not been previously described. The phenotype is unique, comprising features of typical BVMD with ERG and peripheral findings, suggestive of a panretinal dysfunction.