Screening the pathogenic causes of congenital cataract via whole exome sequencing technology in three families: <br />Molecular genetics of congenital cataract

Qi,Chenyang; He,Yunxuan; Jiang,Chun; Zhang,Xiaoxue; Zhu,Peiran; Li,Weiwei; Zhou,Hongjian; Xue,Chunyan; Xia,Xinyi

doi:10.3892/mmr.2023.13008

June-2023 Volume 27 Issue 6

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June-2023 Volume 27 Issue 6

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Article Open Access

Screening the pathogenic causes of congenital cataract via whole exome sequencing technology in three families:
Molecular genetics of congenital cataract

Authors:
- Chenyang Qi
- Yunxuan He
- Chun Jiang
- Xiaoxue Zhang
- Peiran Zhu
- Weiwei Li
- Hongjian Zhou
- Chunyan Xue
- Xinyi Xia
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Affiliations: College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210002, P.R. China, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China, Department of Ophthalmology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China

Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 121
|
Published online on: May 10, 2023

https://doi.org/10.3892/mmr.2023.13008
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Abstract

Congenital cataract is the commonest cause of visual impairment and blindness in children worldwide. Among congenital cataract cases, ~25% are caused by genetic defects, while several genetic mutations have been identified in hereditary cataract. In the present study, a patient with cataract underwent clinical ophthalmic examination and pedigree analysis. Whole exome sequencing and Sanger sequencing were performed to identify and verify gene mutations. The frequency, conservation, pathogenicity and hydrophobicity of the mutated amino acids were analyzed by bioinformatics analysis. The clinical examination and investigation verified that the probands of family A and C suffered from nuclear cataracts. In addition, the proband of family B was diagnosed with white punctate opacity. The pattern of inheritance was autosomal dominant. The sequencing analysis results revealed a mutation c.592-c593insG (p.W198Wfs*22) in exon 6 of CRYBA1/A3, a known mutation c.463C > T (p.Q155X) in exon 6 of CRYBB2 and a third mutation c.865‑c.866insC (p.T289Tfs*91) in exon 2 of GJA8. Each variant was co‑segregated with disease in family And the mutation frequency in the database was <0.01. It has been reported that the mutation sites are highly conserved among different species, thus greatly affecting the sequence and structure of a protein, while exhibiting high pathogenicity in theory. The two crystallin gene mutations could notably enhance the local hydrophobicity of the protein, eventually resulting in its reduced solubility and destruction of lens transparency. The current study identified pathogenic genes in three families with congenital cataract and analyzed the association between mutation sites and different cataract phenotypes. Overall, the results could expand the genotype spectrum of congenital cataract and provide evidence for its clinical diagnosis.

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