Clinical and Mutation Analysis of Patients with Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy in Chinese Population.

Tingting Gao,Lvzhen Huang,Chengqiang Tian,Zhiming Liu,Qinrui Hu,Jimei Zou,Mingwei Zhao

doi:10.1155/2018/4582816

Abstract

Mutations in the gene BEST1 usually cause bestrophinopathies, such as the rare progressive diseases Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). This study aimed to investigate the clinical characteristics of patients with BVMD or ARB carrying BEST1 mutations. A total of 12 probands including 9 patients with a clinical diagnosis of BVMD and 3 patients with a clinical diagnosis of ARB were recruited for genetics analysis. All patients underwent detailed ophthalmic examination. All coding exons of the BEST1 gene were screened by PCR-based DNA sequencing. Programs of PolyPhen-2, SIFT, and MutationTaster were used to analyze the potential pathogenicity of the mutations in BEST1. In the 9 unrelated patients with BVMD, one heterozygous BEST1 mutation was revealed in 8 patients and two compound heterozygous mutations in 1 patient. In the 3 unrelated patients with ARB, two compound heterozygous mutations were revealed in 2 patients and three compound heterozygous mutations in 1 patient. Molecular analyses identified a total of 15 mutations, including 3 novel mutations (c.424A>G p.S142G, c.436G>A p.A146T, and c.155T>C p.L52P). Antivascular endothelial growth factor (VEGF) drugs were given to two affected eyes, especially those also exhibiting choroidal neovascularization (CNV), and no serious adverse events occurred. Our study indicates that there is wide genotypic and phenotypic variability in patients with BVMD or ARB in China. The screening of BEST1 gene is significant for the precise diagnosis of BVMD and ARB.

Highlights

Best vitelliform macular dystrophy (BVMD; OMIM153700) is a maculopathy characterized by the deposition of yellowish, lipofuscin-like or vitelliform lesions that often show considerable morphologic variability in different stages of the disease [1]
8 different mutations were solely detected in patients with BVMD, 6 mutations were solely identified in patients with autosomal recessive bestrophinopathy (ARB), and one missense mutation
The study confirms that BEST1 gene mutation is the primary factor in the development of BVMD and ARB

Summary

Introduction

Best vitelliform macular dystrophy (BVMD; OMIM153700) is a maculopathy characterized by the deposition of yellowish, lipofuscin-like or vitelliform lesions that often show considerable morphologic variability in different stages of the disease [1]. The lesion usually evolves through previtelliform, vitelliform, pseudohypopyon, vitelliruptive, and atrophic/cicatricial stages with time [2]. Electrooculography (EOG) with an Arden ratio of light-peak to dark-trough less than 1.5 is usually a specific clinical diagnostic indicator for BVMD [3]. BVMD is inherited in an autosomal dominant fashion but with variable expressivity [4]. The incidence was noted to be 1.5-20/100000 [5, 6]. The disease was first described by the physician Friedrich Best in 1905 [7]

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