RT Journal Article
SR Electronic
T1 Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP 846
OP 851
DO 10.1136/bjophthalmol-2019-314679
VO 104
IS 6
A1 Feng-Juan Gao
A1 Yu-He Qi
A1 Fang-Yuan Hu
A1 Dan-Dan Wang
A1 Ping Xu
A1 Jing-Li Guo
A1 Jian-Kang Li
A1 Yong-Jin Zhang
A1 Wei Li
A1 Fang Chen
A1 Ge-Zhi Xu
A1 Wei Liu
A1 Qing Chang
A1 Ji-Hong Wu
YR 2020
UL http://bjo.bmj.com/content/104/6/846.abstract
AB Background Bestrophin-1 (BEST1) 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 BEST1 in a large cohort of Chinese patients with bestrophinopathy.Methods Patients clinically suspected of bestrophinopathy were screened using multigene panel testing. All BEST1 variants were confirmed by Sanger sequencing, and validated in the families.Findings 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 BEST1 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%). BEST1 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 BEST1 in our cohort was 71.30%, no de novo mutations were identified.Conclusion This is the largest study to date that provides major population-based data of the BEST1 mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.All data relevant to the study are included in the article or uploaded as supplementary information.