发育迟缓儿童基因组拷贝数变异的遗传学研究

Genetic study on the genomic copy number variation in children with develoopmentaldelay

目的分析发育迟缓患儿基因组拷贝数变异(CNV)检测结果,为患儿明确遗传学病因。方法选取2018年3月—2023年3月就诊于聊城市东昌府区妇幼保健院的发育迟缓儿童260例为研究对象。采用低深度全基因组测序(CNVseq)技术对其进行CNV检测,分析致病/可能致病性CNV的检出情况。结果260例发育迟缓患儿中,共检出致病性CNV 46例、占17.69%,可能致病性CNV 3例、占1.15%,异常检出率为18.85%,意义不明CNV 48例、占18.46%,总阳性率为37.31%。在致病/可能致病性CNV中,检出较多的疾病有:唐氏综合征(7例)、16p11.2缺失综合征(4例)、Angelman/Prader-Willi综合征(4例)、Di George综合征(3例)、9p末端缺失综合征(2例)、猫叫综合征(2例);还检出6例数据库中未定义的综合征或疾病区域的致病性缺失/重复片段。结论CNV是儿童发育迟缓的重要病因,其中缺失占比较大,大片段异常更易致病,可将CNV-seq应用于发育迟缓患儿诊断及产前诊断中,为儿童发育迟缓的临床诊断提供帮助。

Objective To analyze the detection results of genomic copy number variation(CNV)in children with developmental delay,to identify genetic causes for the affected children.Methods From March 2018 to March 2023,260 children with developmental delay who treated in Liaocheng Dongchangfu District Maternal and Child Health Hospital were selected as the research subjects,and CNV was detected by lowdepth whole genome sequencing(CNV-seq)technology,and the detection condition of pathogenic/possibly pathogenic CNV was analyzed.Results Among 260 children with developmental delay,a total of 46 cases of pathogenic CNV were detected,accounting for 17.69%,and 3 cases were possibly pathogenic CNV,accounting for 1.15%,the abnormal detection rate was 18.85%,and 48 cases of CNV with unknown significance were detected,accounting for 18.46%,the total positive rate was 37.31%.Among the pathogenic/possibly pathogenic CNV,the most commonly detected diseases include Down syndrome(7 cases),16pl1.2 deletion syndrome(4 cases),Angelman/Prader-Willi syndrome(4 cases),DiGeorge syndrome(3 cases),9p terminal deletion syndrome(2 cases)and cri-du-chat syndrome(2 cases);6 cases of undefined syndrome or disease regions with pathogenic deletions/duplications fragments not defined in the database were also detected.Conclusion CNV was an important cause of children's developmental delay,in which deletion accounted for a large proportion,and large fragment abnormality was more likely to cause disease.CNV-seq could be applied to the diagnosis and prenatal diagnosis of children with developmental delay and prenatal diagnosis,in order to provide assistance for the clinical diagnosis of children with developmental delay.