ADGRG1基因变异导致巨脑回畸形1例患儿的遗传学分析  

Genetic analysis of a child with pachygyria due to variant of ADGRG1 gene

作　　者：宋传路 苏景玉 Song Chuanlu;Su Jingyu(Genetic Science and Medical Genetics Laboratory,Qinzhou Maternal and Child Health Care Hospital,Qinzhou,Guangxi 535099,China;Central Laboratory for Genetic and Metabolic Diseases,Maternity and Child Health Care Hospital of Guangxi Zhuang Autonomous Region,Nanning,Guangxi 530021,China)

机构地区：[1]钦州市妇幼保健院基因科学与遗传医学实验室,钦州535099 [2]广西壮族自治区妇幼保健院遗传代谢中心实验室,南宁530021

出　　处：《中华医学遗传学杂志》2024年第9期1105-1109,共5页Chinese Journal of Medical Genetics

基　　金：广西壮族自治区卫生健康委员会自筹科研项目(Z-A20220277)。

摘　　要：目的探讨1例巨脑回畸形患儿及其家系成员的遗传学病因。方法选取2020年6月因"智力障碍、巨脑回畸形"就诊于钦州市妇幼保健院的1例巨脑回畸形女性先证者及其家庭成员(共2代4人)为研究对象,回顾性分析先证者临床资料。对先证者进行全外显子组测序(WES)检测候选变异位点,采用Sanger测序家系验证变异位点。本研究通过钦州市妇幼保健院医学伦理委员会的审查(伦理号:20220710)。结果先证者为4岁6月龄女性,临床诊断为巨脑回畸形。WES检测先证者ADGRG1基因存在第6外显子c.781G>T(p.E261*)和第11外显子c.1369A>C(p.S457R)复合杂合变异,Sanger测序验证二者分别来自母亲和父亲。先证者妹妹携带c.1369A>C(p.S457R)杂合变异。根据美国医学遗传学与基因组学学会(ACMG)相关变异评级指南,ADGRG1基因c.781G>T(p.E261*)及c.1369A>C(p.S457R)变异均被评级为可能致病性(PVS1+PM2_Supporting;PM1+PM2_Supporting+PM3+PP3)。结论ADGRG1基因c.781G>T(p.E261*)及c.1369A>C(p.S457R)复合杂合变异可能为该家系患儿巨脑回畸形遗传学病因。ObjectiveTo explore the genetic basis for a child with pachygyria.MethodsA proband who had visited Qinzhou Maternal and Child Health Care Hospital for pachygyria and mental retardation in June 2020 was selected as the study subject.Clinical data was collected.The child was subjected to whole exome sequencing(WES),and candidate variant was verified by Sanger sequencing.This study was approved by the Qinzhou Maternal and Child Health Care Hospital(Ethics No.20220710).ResultsThe proband,a 4-year-old and 6-month-old female,was clinically diagnosed with megagyrus deformity.WES revealed that she has harbored compound heterozygous variants of the ADGRG1 gene,namely c.781G>T(p.E261*)in exon 6 and c.1369A>C(p.S457R)in exon 11,which were verified by Sanger sequencing to be derived from her mother and father,respectively.Her younger sister was also heterozygous for the c.1369A>C(p.S457R)variant.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were rated as likely pathogenic(PVS1+PM2_Supporting;PM1+PM2_Supporting+PM3+PP3).ConclusionThe c.781G>T(p.E261*)and c.1369A>C(p.S457R)compound heterozygous variants of the ADGRG1 gene probably underlay the pachygyria malformation in this child.

关 键 词：皮质发育畸形 Ⅱ组 巨脑回畸形 ADGRG1基因 全外显子组测序 

分 类 号：R725.9[医药卫生—儿科]