Novel BEST1 mutations in Chinese patients with bestrophinopathy

Abstract

Purpose : Bestrophinopathy is a clinically and genetically heterogeneous retinal disease which is mainly caused by BEST1 mutations. The purpose of this study is to analyze the mutation spectrum of BEST1 in a cohort of Chinese bestrophinopathy patients.

Methods : Thirty-five bestrophinopathy patients and 26 clinically healthy family members from 25 unrelated families were recruited. Coding regions and adjacent intronic regions of BEST1 was analyzed by Sanger sequencing.

Results : Ten novel mutations and 13 previous reported mutations were identified. Among the novel mutations, there were 6 missense mutations (c.88A>G, p.K30E; c.500A>G, p.E167G; c.764G>A, p.R255Q; c.817G>A, p.V273M; c.842T>C, p.F281S; and c.380C>T, p.T124M), 1 nonsense mutation (c.1550C>G, p.S157X), 1 deletion mutation (c.950_955del, p.S318_L319) and 2 splicing defects (c.1739+1G>A, c.247+2T>G). All patients had RPE disorder, serous retinal detachment with subretinal vitelliform deposits at the posterior poles (Figure 1-2). Eight patients had angle closure (22.86%) and 21 patients had angle-closure glaucoma (60%).

Conclusions : Ten novel mutations with potential functional consequences were identified in BEST1 in a cohort of Chinese bestrophinopathy patients with high rate of angle closure and angle-closure glaucoma, suggesting a potential genetic and phenomic diversity of bestrophinopathy in Chinese patients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Figure 1. The fundus color photographs, OCT images and sequence maps of 6 autosomal recessive bestrophinopathy (ARB) patients with novel mutations in BEST1. All patients had macular cystoid edema, RPE irregularity, serous retinal detachment with subretinal vitelliform deposits at the posterior poles. Patient 1,2,3 and 6 had pale optic disc with cup/disc ratio increased.

 

Figure 2. The fundus color photographs, OCT images and sequence maps of 3 Best vitelliform macular dystrophy (BVMD) patients with novel mutations in BEST1. Patient 7 had macular cystoid edema, serous retinal detachment with subretinal vitelliform deposits at the posterior pole. Patient 8 had atrophy of outer layer retina at macular. Patient 9 had retinal detachment and cicatricial change at macular.