Clinical Science
Gene mutation analysis of 12 families with congenital cataract
Bai Zhouxian, Shao Jingzhi, Liu Lina, Kong Xiangdong
Published 2022-10-10
Cite as Chin J Exp Ophthalmol, 2022, 40(10): 960-965. DOI: 10.3760/cma.j.cn115989-20200408-00246
Abstract
ObjectiveTo analyze the clinical manifestations of congenital cataract in 12 families and gene variants causing the disease.
MethodsThe method of pedigree investigation was adopted.Clinical data of 27 patients from 12 Chinese Han families with congenital cataract were collected, and genomic DNA was extracted from peripheral blood samples of patients and family members.Candidate variants were screened by next generation sequencing and were verified by Sanger sequencing.Population frequency of the variants were obtained through the Genome Arrgregation Database (gnomAD).Pathogenicity of variants was analyzed through the Human Gene Mutation Database (HGMD), Database of Single Nucleotide Polymorphism (dbSNP) and PubMed, and the mutation effect was interpreted by protein prediction softwares including SIFT, PolyPhen_2 and MutationTaster.The conservation analysis of amino acid sequences of variants was performed by GERP+ + software.Diagnosis was confirmed by clinical ophthalmic phenotype, medical history and mutation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.KS-2018-KY-36).Written informed consent was obtained from all subjects and their guardians.
ResultsPathogenic genetic variants were found in all the 12 families, 9 of which had known pathogenic variants including MIP c.97C>T, GJA8 c.593G>A, CRYBA4 c.277T>C, CRYBB2 c.563G>A and c.436G>C, CRYGC c.470G>A, CRYGD c.70C>A, PAX2 c.70dupG as well as OCRL E5-E16dup, and 3 novel potential pathogenic variants including CRYGD c.422delG, ELP4 c.886C>A and CRYBB2 c.434G>C.CRYGD c.422delG could lead to the early termination of translation of protein products, which was pathogenic.The nucleotide and amino acid sites of ELP4 c.886C>A and CRYBB2 c.434G>C were highly conserved among species, and were predicted as harmful.The 12 families were consistent with co-segregation.
ConclusionsCRYGD c.422delG, ELP4 c.886C>A and CRYBB2 c.434G>C may be novel pathogenic variants of congenital cataract.
Key words:
Cataract, congenital; Gene mutation; Targeted sequencing; Molecular diagnosis
Contributor Information
Bai Zhouxian
Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Shao Jingzhi
Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Liu Lina
Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Kong Xiangdong
Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
