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Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy
  1. Feng-Juan Gao1,2,3,
  2. Yu-He Qi1,2,3,
  3. Fang-Yuan Hu1,2,3,
  4. Dan-Dan Wang1,2,3,
  5. Ping Xu1,2,3,
  6. Jing-Li Guo1,2,3,
  7. Jian-Kang Li4,5,
  8. Yong-Jin Zhang1,2,3,
  9. Wei Li4,6,
  10. Fang Chen4,7,8,
  11. Ge-Zhi Xu1,2,3,
  12. Wei Liu1,2,
  13. Qing Chang1,2,3,
  14. Ji-Hong Wu1,2,3
  1. 1 Eye Institute, EENT hospital of Fudan University, Shanghai, China
  2. 2 Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, Shanghai, China
  3. 3 Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, China, ShangHai
  4. 4 BGI-Shenzhen, Shenzhen, China
  5. 5 Dept of Computer Science, City University of Hong Kong, Kowloon, Hong Kong, China
  6. 6 BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China
  7. 7 Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  8. 8 Shenzhen Engineering Laboratory for Birth Defects Screening, BGI-Shenzhen, Shenzhen, China
  1. Correspondence to Professor Ji-Hong Wu, Ophthalmology, EENT Hospital of Fudan University, Shanghai, China; jihongwu{at}; Professor Qing Chang; qngchang{at}


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.

  • bestrophinopathy
  • next-generation sequencing
  • BEST1
  • mutation spectrum
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  • F-JG and Y-HQ are joint first authors.

  • Contributors J-HW and QC conceived and designed the experiments. G-ZX, WL, J-LG, QC, F-JG, J-HW, Y-JZ, PX and Y-HQ collected the clinical samples. F-JG, J-HW, F-YH, J-KL, WL, FC and D-DW analysed sequencing data. J-LG, WL and Y-HQ performed clinical examination of patients and clinical interpretation. F-JG, Y-HQ and J-HW drafted and revised the manuscript. All authors read and approved the manuscript.

  • Funding This work was supported by the National Natural Science Foundation of China (Grant NSFC81770925, 81770944,81790641, the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences 2018PT32019). The Natural Science Foundation of Guangdong Province (NO.2015A030313472), Shenzhen Engineering Laboratory for Birth Defects Screening, DRC-SZ [2016]750.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained.

  • Ethics approval The current study involving human subjects was approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University, Shanghai, China.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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