Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy.

Abstract

Bestrophin-1 (<i>BEST1</i>) gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum of <i>BEST1</i> in a large cohort of Chinese patients with bestrophinopathy. Patients clinically suspected of bestrophinopathy were screened using multigene panel testing. All <i>BEST1</i> variants were confirmed by Sanger sequencing, and validated in the families. A total of 92 patients (Best vitelliform macular dystrophy (BVMD)=77; autosomal recessive bestrophinopathy (ARB)=15) from 58 unrelated families of Chinese origin and their available family members (n=65) were recruited. Overall, 39 distinct disease-causing <i>BEST1</i> variants were identified, including 13 novel variants, and two reported variants but novel for ARB. Of them, 14 were associated with ARB, 23 with BVMD and two (c.604C>T and c.898G>A) with both BVMD and ARB. Most mutations associated with BVMD were missense (97.78%), while ARB was associated with more complex mutations, including missense (88.46%), splicing effect (3.85%), and frameshifts (15.38%). <i>BEST1</i> hotspots were c.898G>A and c.584C>T among BVMD and ARB patients, respectively. Hot regions were located in exons 8, 2 and 6 in BVMD patients, and in exons 5 and 7 in ARB patients. The overall penetrance of <i>BEST1</i> in our cohort was 71.30%, no de novo mutations were identified. This is the largest study to date that provides major population-based data of the <i>BEST1</i> mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.