摘要
目的探讨全外显子组测序(WES)对于智力障碍(ID)或全面发育迟缓(GDD)患者的诊断价值。方法选取2018年5月至2021年12月于郴州市第一人民医院就诊的134例ID或GDD患者为研究对象。采集患者及其父母的外周血样进行WES检测,对候选变异进行Sanger测序/拷贝数变异测序(CNV-seq)验证和家系来源分析,对候选变异根据美国医学遗传学与基因组学学会(ACMG)变异分类标准进行致病性评估。结果在134例患者中,共检出致病性单核苷酸变异(SNV)及小片段插入/缺失(InDel)46例,致病性基因组拷贝数变异(CNV)11例,单亲二倍体(UPD)1例,总体阳性检出率为43.28%(58/134)。46例致病性SNV/InDel共涉及40个基因62个位点,其中最多的是MECP2基因(n=4)。11例致病性CNV中,10例为缺失变异,1例为重复变异,片段范围为0.76~15.02 Mb。1例患者在15q11.2q12区存在约15.62 Mb的杂合性丢失(LOH),结合家系WES数据提示为父源性UPD,结合其临床表型诊断为Angelman综合征。结论WES不仅能够高效检出SNV/InDel,对CNV、LOH也有较高的检出率,结合家系数据分析能够准确判断变异的来源,这些优势表明WES对ID或GDD患者的遗传学病因诊断具有重要的价值。
Objective To assess the diagnostic value of whole exome sequencing(WES)for patients with intellectual disability(ID)or global developmental delay(GDD).Methods 134 individuals with ID or GDD who presented at Chenzhou First People′s Hospital between May 2018 and December 2021 were selected as the study subjects.WES was carried out on peripheral blood samples of the patients and their parents,and candidate variants were verified by Sanger sequencing,copy number variation sequencing(CNV-seq)and co-segregation analysis.The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).Results A total of 46 pathogenic single nucleotide variants(SNVs)and small insertion/deletion(InDel)variants,11 pathogenic genomic copy number variants(CNVs),and 1 uniparental diploidy(UPD)were detected,which yielded an overall detection rate of 43.28%(58/134).The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes,among which MECP2 was the most frequent(n=4).The 11 pathogenic CNVs have included 10 deletions and 1 duplication,which have ranged from 0.76 to 15.02 Mb.A loss of heterozygosity(LOH)region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient,which was validated as paternal UPD based on the result of trio-WES.The patient was ultimately diagnosed as Angelman syndrome.Conclusion WES can detect not only SNV/InDel,but also CNV and LOH.By integrating family data,WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.
作者
李阳艳
雷冬竹
李彩云
黄东群
谭菊芳
张昊晴
Li Yangyan;Lei Dongzhu;Li Caiyun;Huang Dongqun;Tan Jufang;Zhang Haoqing(Center of Prenatal Diagnosis,Chenzhou Hospital Affiliated to Hengyang Medical School,University of South China,Hengyang,Hunan 421001,China;Center of Prenatal Diagnosis,Chenzhou First People′s Hospital,Chenzhou,Hunan 423000,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2023年第6期648-654,共7页
Chinese Journal of Medical Genetics
基金
湖南省临床医疗技术创新引导项目(2020SK50301、2020SK50309)
湖南省科技创新平台与人才计划(2020SK4023)
郴州市重点研发及技术创新引导专项(ZDYF2020019)。
