June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Comprehensive Genetic Analysis Unraveled the Missing Heritability in a Chinese Cohort With Autosomal Recessive Bestrophinopathy
Author Affiliations & Notes
  • Jie Shi
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Yang Li
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Xiaohui Zhang
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Xin Zhang
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • tian lu
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Yue Xie
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Xu Ke
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, Beijing, China
  • Footnotes
    Commercial Relationships   Jie Shi None; Yang Li None; Xiaohui Zhang None; Xin Zhang None; tian lu None; Yue Xie None; Xu Ke None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4524. doi:
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    • Get Citation

      Jie Shi, Yang Li, Xiaohui Zhang, Xin Zhang, tian lu, Yue Xie, Xu Ke; Comprehensive Genetic Analysis Unraveled the Missing Heritability in a Chinese Cohort With Autosomal Recessive Bestrophinopathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4524.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To identify the missing heritability of autosomal recessive bestrophinopathy (ARB) in a Chinese cohort and to report a founder variant of BEST1.

Methods : We recruited 63 unrelated patients with a clinical diagnosis of ARB. All patients underwent ophthalmic examinations and comprehensive genetic analyses including Sanger-DNA sequencing of BEST1 and next-generation sequencing of the whole BEST1 sequence.

Results : We identified 56 distinct disease-causing variants of BEST1 in 63 patients, 62 patients with biallelic variants, and one patient with a monoallelic variant. Sanger-DNA sequencing of BEST1 initially detected 53 variants in 61 probands and 19 of them were identified with single heterozygous variants. Subsequent whole genome sequencing combined with supplementary Sanger sequencing revealed three missing deep intronic variants (DIVs) in 20 patients: c.1101-491A>G, c.867+97G>A, c.867+97G>T. Minigene assays showed that the c.1101-491A>G activated cryptic splice sites and led to the insertion of pseudoexons, but no aberrant splicing product in assays of c.867+97G>A/T. The c.867+97G>A is a missense variant in another alternative transcript ENST00000526988 as c.646G>A (p.V216I), which was identified as a founder effect with the highest allele frequency (16%).

Conclusions : Our results expand the pathogenic variant spectrum of BEST1. DIVs and alternative transcript variation explained the missing heritability of ARB. The variant c.867+97G>A, also known as c.646G>A (p.V216I) in transcript ENST00000526988, is a founder variant in Chinese patients with ARB.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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