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

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.

Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases

“…Our work expands the pathogenic mutation spectrum of BEST1 associated with ARB and the clinical features of the disease, leading to improved diagnosis and genetic counseling criteria for affected patients and their families. In our study, missense mutations were the leading cause of ARB (5/7, 71%), which is in concordance with other reported cases [ 19 – 23 ].…”

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

“…Many studies, including this one, have attempted to determine genotype-phenotype correlations of Bestrophinopathy, but the evidence is limited [10,15]. However, we found that the homozygous BEST1 mutation spectrum has certain clinical characteristics, the most common being extrafoveal and extramacular yellowish subretinal deposits.…”

Disease expression caused by different variants in the BEST1 gene: genotype and phenotype findings in bestrophinopathies

“…2008; Gao et al. 2018). Retinal oedema and neurosensory retinal detachment with subretinal fluid can be observed, and no vitelliform lesions develop 5 .…”

“…2012; Gao et al. 2018), and they have been investigated in several different ethnic groups (Italian, Dutch, Swedish, German, Chinese, Australian) (Deutman 1971; Tian et al. 2017; Gao et al.…”