山西医科大学学报2025，Vol.56Issue(2)：200-207,8.DOI:10.13753/j.issn.1007-6611.2025.02.013
AFG2A基因新发复合杂合变异导致罕见NEDHSB一家系分析并文献复习
A pedigree analysis of rare NEDHSB caused by a novel compound heterozygous variants in the AFG2A gene and literature review
摘要
Abstract
Objective To analyze the genetic variation characteristics and clinical phenotypes of a family with neurodevelopmental disorder with hearing loss,seizures,and brain abnormalities(NEDHSB)caused by a new compound heterozygous variants in the AFG2A gene,and provide a reference for genetic counseling and prenatal diagnosis.Methods Clinical data of the proband,his sister and his parents were collected and analyzed.The child,his sister,and their parents were tested by whole exome sequencing(WES),the sites were validated by Sanger sequencing,and the hazard of their compound heterozygous variants was predicted.Literature review was conducted through domestic and international databases to collect reported cases of AFG2A gene variants.Results The proband in the family exhibited developmental epileptic encephalopathy,while the sister of the proband had no clinical manifestations to date.The proband had a missense variant c.1678G>A(p.Val560Ile)and a newly discovered frameshift variant c.544delA(p.Thr182fsTer14)in the AFG2A gene.The c.1678G>A variant was inherited from the father,and the c.544delA variant was inherited from the mother.The sister of the proband was a carrier of the c.1678G>A(p.Val560Ile)missense variant in the AFG2A gene.According to the American College of Medical Genetics and Genomics(ACMG)variant classification guidelines,the c.1678G>A(p.Val560Ile)site was a variant of uncertain significance(VUS),and the c.544delA(p.Thr182fsTer14)site was likely to be pathogenic(LP).The c.544delA site was a newly discovered frameshift site variant,and software prediction indicated that this variant resulted in loss of gene function.Upon reviewing domestic and international literature,there were 38 cases of NEDHSB,among which 7 patients exhibited frameshift site variant.However,the variant discovered in this study was not documented previously.Conclusion The frameshift site variant in AFG2A is newly reported,which enriches the spectrum of AFG2A gene variants.The novel compound heterozygous variant of c.1678G>A and c.544delA in the AFG2A gene is the pathogenic cause of the proband in this family.关键词
AFG2A基因/NEDHSB/新发变异/全外显子测序/遗传学分析/生物信息学分析/癫痫性脑病Key words
AFG2A gene/neurodevelopmental disorders/novel genetic variation/whole exome sequencing/genetic analysis/bioinformatics analysis/epileptic encephalopathy分类
医药卫生引用本文复制引用
岳昊,郭敏,赵晨玥,高景波,郭荣,曹桂芝,薛慧琴..AFG2A基因新发复合杂合变异导致罕见NEDHSB一家系分析并文献复习[J].山西医科大学学报,2025,56(2):200-207,8.基金项目
复杂遗传病远程协同服务网示范应用(SJPT-03-16) （SJPT-03-16）
山西省回国留学人员科研教研资助项目(2023-180) （2023-180）
山西省"四个一批"科技兴医创新计划项目医学遗传学研究委级重点实验室建设项目(2021SYS24) （2021SYS24）
山西省卫生健康委员会资助项目(2023016) （2023016）
