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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Feng-Juan Gao
  • Yu-He Qi
  • Fang-Yuan Hu
  • Dan-Dan Wang
  • Ping Xu
  • Jing-Li Guo
  • Yong-Jin Zhang
  • Wei Li
  • Fang Chen
  • Ge-Zhi Xu
  • Wei Liu
  • Qing Chang
  • Ji-Hong Wu

Related Research Unit(s)

Detail(s)

Original languageEnglish
Journal / PublicationBritish Journal of Ophthalmology
Online published13 Sep 2019
Publication statusOnline published - 13 Sep 2019

Abstract

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.

Research Area(s)

  • BEST1, bestrophinopathy, mutation spectrum, next-generation sequencing

Citation Format(s)

Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy. / Gao, Feng-Juan; Qi, Yu-He; Hu, Fang-Yuan; Wang, Dan-Dan; Xu, Ping; Guo, Jing-Li; Li, Jian-Kang; Zhang, Yong-Jin; Li, Wei; Chen, Fang; Xu, Ge-Zhi; Liu, Wei; Chang, Qing; Wu, Ji-Hong.

In: British Journal of Ophthalmology, 13.09.2019.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal