汉族毛囊角化病一个家系的临床表型及遗传学分析  

Analysis of clinical feature and genetic variant in a Chinese Han pedigree affected with Darier′s disease

作　　者：张士德 姜淼[2] 林榕 金佳慧 赵敬军 Zhang Shide;Jiang Miao;Lin Rong;Jin Jiahui;Zhao Jingjun(Department of Dermatology,Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuding,Fujian 355200,China;Department of Dermatology,Tongji Hospital of Tongji University,Shanghai 200065,China;Department of Laboratory Medicine,Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuding,Fujian 355200,China;Department of Dermatology,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]福建中医药大学附属福鼎医院皮肤科,福鼎355200 [2]同济大学附属同济医院皮肤科,上海200065 [3]福建中医药大学附属福鼎医院检验科,福鼎355200 [4]上海交通大学医学院附属新华医院皮肤科,上海200092

出　　处：《中华医学遗传学杂志》2025年第2期206-211,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(82072258,82373482);上海市卫健委临床研究项目(202240346)。

摘　　要：目的探讨1个汉族毛囊角化病(DD)家系的临床表型与遗传学特征。方法选取2023年10月22日就诊于同济大学附属同济医院的1个DD家系为研究对象。收集该家系临床资料,对先证者进行全基因组外显子测序,筛选可疑变异位点后对家系成员进行Sanger测序验证,并对变异位点进行生物信息学分析。本研究已通过同济大学附属同济医院医学伦理委员会的审查(批准号:K-W-2024-004)。结果①先证者为67岁女性,具有DD临床特点如皮脂溢出部位角化性丘疹。②全基因组外显子测序显示先证者ATP2A2基因第1外显子存在c.68G>A(p.Gly23Glu)错义变异;Sanger测序提示先证者长女同样携带该变异,家系其他成员未检测到该变异,提示该变异与家系疾病表型存在共分离现象。③参照美国医学遗传学与基因组学学会(ACMG)关于基因变异位点的解读原则,该变异被判定为致病性(PS1+PM1+PM2_(S)upporting+PP1+PP3+PP4)。结论ATP2A2基因c.68G>A(p.Gly23Glu)变异可能是该家系的遗传学病因,进一步丰富了DD患者基因变异谱,为DD患者的临床诊断和遗传咨询提供了依据。ObjectiveTo explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier′s disease(DD).MethodsA DD pedigree,who visited Tongji Hospital of Tongji University on October 22,2023,was selected as the study subject.Clinical data of the pedigree were collected,and whole-genome exom sequencing was performed on the proband.Suspected variant loci were screened,and Sanger sequencing was used to validate the variant in pedigree members.Bioinformatics analysis was performed on the variant loci.This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University(Ethics No.K-W-2024-004).Results①The proband is a 67-year-old female with clinical features of DD,such as keratotic papules in sebaceous areas.②Whole-genome exom sequencing revealed a missense variant,c.68G>A(p.Gly23Glu),in the exon 1 of ATP2A2 gene of the proband.Sanger sequencing showed that the proband′s eldest daughter also carried this variant.This variant was not detected in other pedigree members,indicating a co-segregation of the variant with the disease phenotype in the pedigree.③According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics(ACMG),this variant was classified as pathogenic(PS1+PM1+PM2_Supporting+PP1+PP3+PP4).ConclusionsThe c.68G>A(p.Gly23Glu)variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree.This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.

关 键 词：毛囊角化病 ATP2A2基因 基因变异 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]