SCN9A基因复合杂合变异所致先天性无痛症1例患儿的遗传学分析  

Genetic analysis of a child with Congenital insensitivity to pain due to compound heterozygous variants of SCN9A gene

作　　者：谭晓兰 杨元[1] 刘运强[1] Tan Xiaolan;Yang Yuan;Liu Yunqiang(Department of Medical Genetics,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西医院医学遗传中心,成都610041

出　　处：《中华医学遗传学杂志》2024年第11期1344-1348,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81773159)。

摘　　要：目的探讨1例表现为多次骨折、疼痛不敏感的患儿的遗传学病因。方法以1例因反复骨折、对疼痛不敏感于2023年3月16日就诊于四川大学华西医院的患儿作为研究对象。收集患儿及其父母的外周血样,对其进行家系全外显子组测序,对候选变异进行Sanger测序验证和致病性分析。本研究通过了四川大学华西医学伦理委员会的审查[伦理号:2019年审(772)号]。结果患儿SCN9A基因存在c.829C>T(p.R277*)和c.560delC(p.P187Rfs*15)复合杂合变异,分别遗传自其父母。其中c.829C>T(p.R277*)纯合变异为先天性无痛症的已知致病变异。根据美国医学遗传学与基因组学学会相关指南,c.560delC(p.P187Rfs*15)被判定为致病性变异。结论患儿被确诊为SCN9A基因复合杂合变异所致的先天性无痛症。上述结果为其家系成员的再生育提供了依据。Objective To explore the genetic etiology of a child featuring multiple fractures and congenital insensitivity to pain(CIP).Methods A child who had presented at the West China Hospital of Sichuan University on March 16,2023 for recurrent fractures and CIP was selected as the study subject.Peripheral blood samples of the child and his parents was collected.Trio-whole exome sequencing was carried out.Candidate variants were verified by Sanger sequencing and bioinformatic analysis.This study has been approved by the Medical Ethics Committee of West China Hospital of Sichuan University(No.2019-772).Results Trio-whole exome sequencing revealed that the child has harbored compound heterozygous variants of the SCN9A gene,namely c.560delC(p.P187Rfs*15)and c.829C>T(p.R277*),which were respectively inherited from his father and mother.Homozygous c.829C>T variant had been demonstrated as pathogenic among CIP patients,whilst the c.560delC(p.P187Rfs*15)variant was unreported previously and predicted to be pathogenic based on the guidelines of the American College of Medical Genetics and Genomics(ACMG).Conclusion The child was diagnosed with CIP due to the compound heterozygous variants of the SCN9A gene.Above finding has enabled genetic counselling and reproductive guidance for this family.

关 键 词：先天性无痛症 SCN9A基因 复合杂合变异 

分 类 号：R725.9[医药卫生—儿科]