Genetic and clinical features of BEST1-associated retinopathy based on 59 Chinese families and database comparisons

Wang, Yingwei; Jiang, Yi; Li, Xueqing; Xiao, Xueshan; Li, Shiqiang; Sun, Wenmin; Wang, Panfeng; Zhang, Qingjiong

doi:10.1016/j.exer.2022.109217

Cited by 2 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 54 distinct variants identified in this study comprised all types of pathogenic BEST1 variants, except for copy number variations, which were only reported in three patients. 12 , 19 , 20 Most variants (67%) were missense, in agreement with our previous observations and several other studies (58%–88%) 9 , 10 , 21 – 23 ; however, this percentage of missense variants identified in patients with ARB was much lower than the percentage (94.7%–100%) detected in patients with BVMD. 9 , 10 , 23 The variants detected in our cohort were mainly clustered in three hotspot regions: codons 12 to 52, 184 to 205, and 253 to 312.…”

Section: Discussionsupporting

confidence: 92%

“… 12 , 19 , 20 Most variants (67%) were missense, in agreement with our previous observations and several other studies (58%–88%) 9 , 10 , 21 – 23 ; however, this percentage of missense variants identified in patients with ARB was much lower than the percentage (94.7%–100%) detected in patients with BVMD. 9 , 10 , 23 The variants detected in our cohort were mainly clustered in three hotspot regions: codons 12 to 52, 184 to 205, and 253 to 312. These hotspots differed from the four well-known hot regions for BVMD described previously by Krämer et al 24 In the current cohort, the most common variant was c.867+97G>A, with an allele frequency of 16%.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy

Shi,

Tian,

Sun

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose To describe the genetic landscape of BEST1 for a large Chinese cohort with autosomal recessive bestrophinopathy (ARB), identify the missing heritability, and report a common Chinese founder variant. Methods We recruited 65 patients from 63 families with a clinical diagnosis of ARB. All patients underwent ophthalmic examinations and comprehensive genetic analyses, including Sanger DNA sequencing of BEST1 and whole genome sequencing (WGS). The effects of deep intronic variants (DIVs) on splicing were assessed using in vitro splicing assays in HEK293T cells and patient-derived peripheral blood mononuclear cells. Haplotype mapping was performed for 17 unrelated patients harboring variant c.867+97G>A. Results We identified 54 distinct disease-causing variants of BEST1 in 63 pedigrees, 62 probands with biallelic variants, and one family with monoallelic variants. Sanger DNA sequencing of BEST1 initially detected 51 variants in 61 pedigrees, including 19 probands with one heterozygous variant. Subsequent WGS, combined with supplementary Sanger sequencing, revealed three missing DIVs (c.1101-491A>G, c.867+97G>A, and c.867+97G>T) in 20 families. The novel DIV c.1101-491A>G caused an abnormal splicing resulting in a 204-nt pseudoexon (PE) insertion, whereas c.867+97G>A/T relatively strengthened an alternative donor site, resulting in a 203-nt intron retention (IR). The PE and IR generated a premature termination codon downstream. Haplotype analysis identified c.867+97G>A as a common founder variant with an allele frequency of 16%. Conclusions Our results expand the pathogenic variant spectrum of BEST1 , and DIVs can explain almost all of the missing heritability. The c.867+97G>A DIV is a common founder variant for Chinese patients with ARB.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy

Shi,

Tian,

Sun

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications

Xu,

Zou,

Yin

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Ion channels in retinal pigment epithelial (RPE) cells are crucial for retinal health and vision functions. Defects in such channels are intricately associated with the development of various retinopathies that cause blindness. Human pluripotent stem cells (hPSC)-derived RPE cells, including those from human-induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hESC), have been used as in vitro models for investigating pathogenic mechanisms and screening potential therapeutic strategies for retinopathies. Therefore, the cellular status of hPSC-RPE cells, including maturity and physiologic functions, have been widely explored. Particularly, research on ion channels in hPSC-RPE cells can lead to the development of more stable models upon which robust investigations and clinical safety assessments can be performed. Moreover, the use of patient-specific hiPSC-RPE cells has significantly accelerated the clinical translation of gene therapy for retinal channelopathies, such as bestrophinopathies. This review consolidates current research on ion channels in hPSC-RPE cells, specifically Kir7.1, Bestrophin-1, CLC-2, and Ca V 1.3, providing a foundation for future research. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-024-05769-5.

show abstract

Genetic and clinical features of BEST1-associated retinopathy based on 59 Chinese families and database comparisons

Cited by 2 publications

References 43 publications

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy

Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications

Contact Info

Product

Resources

About