Novel BEST1 mutations and special clinical characteristics of autosomal recessive bestrophinopathy in Chinese patients

Abstract

Purpose: The aim of this study was to describe the genetic and clinical characteristics of Chinese patients with autosomal recessive bestrophinopathy (ARB). Methods: This study presents a retrospective observational case series. Twentyone ARB patients and 25 clinically healthy family members were recruited. The coding regions and adjacent intronic regions of BEST1 were analysed via Sanger sequencing. Clinical examinations, including ultrasound biomicroscopy, A-scan, optical coherence tomography, fundus autofluorescence, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and visual electrophysiology, were reviewed. Results: Six novel mutations (c.380C>T, p.T127M; c.397A>G, p.N133D; c.500A>G, p.E167G; c.817G>A, p.V273M; c.174_176del, p.Q58del; and c.950_955del, p.S318_L319) and 8 previously reported mutations were identified. The p.R255W mutation had the highest frequency in our cohort. Twenty patients had serous retinal detachment with multifocal subretinal vitelliform deposits in the posterior poles. One patient exhibited chorioretinal atrophy. FFA revealed peripheral vascular leakage in 10 patients, and ICGA revealed hyperfluorescent spots in 8 patients. Visual electrophysiology was abnormal in all patients. Fifteen patients with angle closure (AC) or angle-closure glaucoma (ACG) had shallower anterior chambers and shorter axial lengths than the patients with open angle, contributing to their risk of developing AC/ACG. One patient developed AC during the 7-year follow-up period. The misdiagnosis and missed rates were 35.3% and 58.8%, respectively. Conclusion: The six novel mutations and high frequency of p.R255W suggest ethnical differences in the BEST1 mutation spectrum among Chinese patients. BEST1 gene screening and detailed clinical examinations help establishing a diagnosis of ARB. Clinical evaluations of the risk of developing AC/ACG are recommended for ARB patients.

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

“…Seven variants in BEST1 were detected, including one novel mutation. Missense mutations were the most common mutation type, which was consistent with previous studies [10,14]. Interestingly, we also 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].…”

Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families

“…BVMD is clinically characterized by morphologic variability: the deposition of yellowish, lipofuscin‐like or vitelliform lesions usually evolves through previtelliform, vitelliform with “egg‐yolk,” pseudohypopyon, vitelliruptive with scrambled egg and atrophic stages . Although ARB is considered as a null phenotype of bestrophin‐1 in humans, it displays serous retinal detachment with extramacular vitelliform lesions and it is likely that this form affects the eye development more than BVMD . The most common distinguishing characteristic of ARB is the deposits in the extra foveal and extra macular subretinal matrix…”

Induced Pluripotent Stem Cell Modeling of Best Disease and Autosomal Recessive Bestrophinopathy

“…6 Nearly 40 biallelic mutations in BEST1 have been reported in ARB patients to date. [12][13][14][15] Retinopathy includes an irregularity of the RPE throughout the posterior fundus with punctate flecks, which is easily seen on autofluorescence imaging. Retinal edema and subretinal fluid are common findings on OCT imaging.…”