Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB).

Imen Habibi,Maria Helfenstein,Daniel F. Schorderet,Leila El Matri,Ahmed Turki,Yosra Falfoul,Margarita G. Todorova,Stefan Wyrsch,Khaled El Matri,Veronika Vaclavik

doi:10.3390/genes10120953

Abstract

Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in BEST1. Its frequency is estimated to be 1/1,000,000 individuals. Here we report 6 families and searched for a genotype-phenotype correlation. All patients were referred due to reduced best-corrected visual acuity (BCVA), ranging from 0.1/10 to 3/10. They all showed vitelliform lesions located at the macula, sometimes extending into the midperiphery, along the vessels and the optic disc. Onset of the disease varied from the age of 3 to 25 years. Electrooculogram (EOG) revealed reduction in the EOG light rise in all patients. Molecular analysis revealed previously reported mutations p.(E35K);(E35K), p.(L31M);(L31M), p.(R141H);(A195V), p.(R202W);(R202W), and p.(Q220*);(Q220*) in five families. One family showed a novel mutation: p.(E167G);(E167G). All mutations were heterozygous in the parents. In one family, heterozygous children showed various reductions in the EOG light rise and autofluorescent deposits. Autosomal recessive Bestrophinopathy (ARB), although rare, can be recognized by its phenotype and should be validated by molecular analysis. Genotype-phenotype correlations are difficult to establish and will require the analysis of additional cases.

Highlights

Bestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as Bestrophinopathy
Of a spectrum of retinal diseases described for the first time by Schatz et al [1,2] as a condition caused by compound heterozygous BEST1 mutations with a modifier effect of the first onto the second mutation
We observed that 4 out of 7 mutations identified in this study were located in exon 5, which is similar to other studies where 53.85% of mutations were located in exons 5 or 7 [12]

Summary

Introduction

Bestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as Bestrophinopathy. Autosomal recessive Bestrophinopathy (ARB) is part of a spectrum of retinal diseases described for the first time by Schatz et al [1,2] as a condition caused by compound heterozygous BEST1 mutations with a modifier effect of the first onto the second mutation. ARB is characterized by different clinical aspects including variable visual loss, hyperopia, angle-closure glaucoma, diffuse yellowish lesions corresponding to subretinal deposits merging over time, macular. Genes 2019, 10, x FOR PEER REVIEW of a spectrum of retinal diseases described for the first time by Schatz et al [1,2] as a condition caused by compound heterozygous BEST1 mutations with a modifier effect of the first onto the second mutation.

Methods

Findings

Discussion

Conclusion