TNFAIP3基因突变导致的1例自身炎症性疾病患者的遗传学分析  

Genetic analysis of a patient with autoinflammatory disease caused by TNFAIP3 gene variant

作　　者：张浩 张乐[1] 马维维[1] 王军[1] 段小龙 ZHANG Hao;ZHANG Le;MA Weiwei;WANG Jun;DUAN Xiaolong(Department of Pediatrics,Hanzhong Central Hospital,Hanzhong,Shaanxi 723000,China)

机构地区：[1]汉中市中心医院儿科,陕西汉中723000

出　　处：《中国优生与遗传杂志》2023年第12期2560-2563,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨分析1个临床表现为自身炎症性疾病患儿的遗传学病因。方法利用家系全外显子组测序(Trio-WES)对患儿及其父母进行遗传学分析,并对潜在的变异位点进行Sanger测序验证。结果Trio-WES检测提示患儿携带TNFAIP3基因NM_006290:c.610A>T(p.Arg204*)杂合变异,其父母均未检测到该变异,理论上为新发变异。Sanger测序与WES结果一致。该变异在人群基因组突变频率数据库(gnomAD)中未见收录,且未见既往文献报道。根据美国医学遗传学与基因组学学会(ACMG)遗传变异分类标准与指南,该变异定义为致病性变异(PVS1+PS2+PM2)。结论本研究通过全外显子组测序确定了TNFAIP3基因无义突变为本例患儿的遗传学病因,丰富了TNFAIP3基因的突变谱和疾病谱,为该家系下一胎的产前诊断提供分子依据。Objective In order to investigate the genetic etiology of a patient with clinical manifestations of autoinflammatory disease.Methods Trio-based whole exome sequencing(Trio-WES)was used to analyze the genetic characteristics of the patient and his parents,and Sanger sequencing was used to verify the potential mutation sites.Results Trio-WES showed that the patient carried a novel heterozygous variant NM_006290:c.610A>T(p.Arg204*)of TNFAIP3 gene,which was not detected in his parents.Sanger sequencing was consistent with WES.This variant was not included in the population genome mutation frequency database(gnomAD)and has not been reported in previous literatures.This variant was defined as a pathogenic variant(PVS1+PS2+PM2)according to the American Academy of Medical Genetics and Genomics(ACMG)criteria and guidelines for the classification of genetic variants.Conclusion This study identified a nonsense variant of TNFAIP3 gene as the genetic cause of this patient through Trio-WES,which enriched the mutation spectrum and disease spectrum of TNFAIP3 gene,and provided genetic counseling for prenatal diagnosis of the next fetus in this family.

关 键 词：TNFAIP3基因 自身炎症性疾病 免疫缺陷 A20单倍计量不足 

分 类 号：R725.9[医药卫生—儿科]