拷贝数变异测序在智力障碍、发育迟缓及孤独谱系综合征的病因学分析中的应用  

Application of copy number variation sequencing in patients with intellectual disability/developmental delay and autistic spectrum disorder

作　　者：雷洁[1] 赵刚 黄彦科[1] 龙敏 李维[1] 邓茜 修子涵 肖砚微 曾思繁 张静[1] Lei Jie;Zhao Gang;Huang Yanke;Long Min;Li Wei;Deng Xi;Xiu Zihan;Xiao Yanwei;Zeng Sifan;Zhang Jing(Department of Clinical Laboratory,Nanshan Maternity and Child Health Care Hospital,Shenzhen,Guangdong 518067,China)

机构地区：[1]深圳市南山区妇幼保健院检验科,深圳518067

出　　处：《中华医学遗传学杂志》2023年第3期308-316,共9页Chinese Journal of Medical Genetics

基　　金：深圳市南山区卫生科技计划(NS2021086)。

摘　　要：目的探讨拷贝数变异测序(CNV-seq)对于智力障碍(ID)、发育迟缓(DD)及孤独谱系障碍(ASD)患儿的诊断价值。方法收集2018年9月至2022年1月在深圳市南山区妇幼保健院诊断为ID、DD及ASD的患儿40例,采集其外周血样,分别进行染色体核型分析和CNV-seq检测,查询ClinVar、DECIPHER、OMIM等数据库并结合生物信息学分析评估拷贝数变异(CNVs)的致病性。结果40例患者检测出ID 16例(40.0%)、DD 15例(37.5%)、ASD 6例(15.0%)、ID合并DD为1例,ID合并ASD为2例。核型分析发现47,XY,+mar、46,XY,inv(8)(p11.2q21.2)、46,XX,del(5)(p14)以及46,XX[76]/46,X,dup(X)(p21.1q12)各1例,染色体多态性2例。CNV-seq在20例患儿中共检出32处CNVs,检出率(50.0%)明显高于核型分析。在10例(25.0%)患儿中发现了致病性CNVs(检出率为25.0%),12例患者中发现了15处意义未明的CNVs(检出率为30.0%),4例患者中发现了7处良性/可能良性的CNVs(检出率为10.0%)。结论基因组CNVs是ID/DD和ASD重要的遗传学病因,CNV-seq可为明确其病因提供重要的参考。Objective To assess the value of copy number variation sequencing(CNV-seq)for the diagnosis of children with intellectual disability(ID),developmental delay(DD),and autistic spectrum disorder(ASD).Methods Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled.G-banded karyotyping analysis was carried out for the patients.Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations(CNVs)in such patients.ClinVar,DECIPHER,OMIM and other database were searched for data annotation.Results Among the 40 patients(including 30 males and 10 females),16,15 and 6 were diagnosed with ID,DD and ASD,respectively.One patient had combined symptoms of ID and DD,whilst the remaining two had combined ID and ASD.Four patients were found with abnormal karyotypes,including 47,XY,+mar,46,XY,inv(8)(p11.2q21.2),46,XX,del(5)(p14)and 46,XX[76]/46,X,dup(X)(p21.1q12).Chromosome polymorphism was also found in two other patients.CNV-seq analysis has detected 32 CNVs in 20 patients(50.0%,20/40).Pathogenic CNVs were found in 10 patients(25.0%),15 CNVs of uncertain clinical significance were found in 12 patients(30.0%),and 7 likely benign CNVs were found in 4 patients(10.0%).Conclusion Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD.CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications,which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.

关 键 词：拷贝数变异 智力障碍 发育迟缓 孤独谱系障碍 测序 

分 类 号：R749.94[医药卫生—神经病学与精神病学]