TY - JOUR
T1 - Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy
AU - Gao, Feng-Juan
AU - Qi, Yu-He
AU - Hu, Fang-Yuan
AU - Wang, Dan-Dan
AU - Xu, Ping
AU - Guo, Jing-Li
AU - Li, Jian-Kang
AU - Zhang, Yong-Jin
AU - Li, Wei
AU - Chen, Fang
AU - Xu, Ge-Zhi
AU - Liu, Wei
AU - Chang, Qing
AU - Wu, Ji-Hong
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
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.
KW - BEST1
KW - bestrophinopathy
KW - mutation spectrum
KW - next-generation sequencing
U2 - 10.1136/bjophthalmol-2019-314679
DO - 10.1136/bjophthalmol-2019-314679
M3 - Journal article
C2 - 31519547
AN - SCOPUS:85072296166
SN - 0007-1161
JO - British Journal of Ophthalmology
JF - British Journal of Ophthalmology
ER -