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 › peer-review
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|Journal / Publication||British Journal of Ophthalmology|
|Online published||13 Sep 2019|
|Publication status||Published - Jun 2020|
|Link to Scopus||https://www.scopus.com/record/display.uri?eid=2-s2.0-85072296166&origin=recordpage|
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.
- BEST1, bestrophinopathy, mutation spectrum, next-generation sequencing
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, Vol. 104, No. 6, 06.2020, p. 846-851.