SNP微阵列和基因捕获测序联合在智力障碍或精神发育迟缓儿童中的应用价值

Application Value of the Combination of SNP Microarray and Gene Capture Sequencing Technology in Children with Intellectual Disabilities or Mental Retardation

目的研究单核苷酸多态性(Single Nucleotide Polymorphism,SNP)微阵列和新一代基因捕获测序技术的联合应用对智力障碍或精神发育迟缓儿童的诊断价值。方法通过资料分析法选取2018年9月至2020年3月在南京医科大学附属儿童医院康复门诊接受治疗的智力障碍或精神发育迟缓儿童19名,年龄在6个月至14岁,男童11人和女童8人。分别采用发育诊断量表和韦氏儿童智力量表中国修订本(WISC-RC)对其进行智力评定,发育商低于49分或智商低于51分者纳入本次研究,进行全基因组拷贝数变异(Copy Number Variation,CNV)及致病基因变异分析,对检测的CNV采用定量PCR法进行先证者及父母验证,对明确或疑似致病性基因变异采用双脱氧法测序进行验证和家庭基因谱核查。结果研究表明19名入选者中有16名患儿的SNP微阵列分析结果为阴性,其中6例确认患有单一遗传疾病、7例阴性、3例存在可疑的基因病变(表现在11q24.1q25、21q22.2q22.3、12q22.1q23区域,其是诱发智力障碍和精神发育迟缓的主要病因)。结论SNP微阵列和新一代基因捕获测序技术的联合应用可显著提高不明原因的智力障碍或精神发育迟缓儿童的分子遗传病因诊断概率,通过寻根朔源方式也可为后续诊治方向提供可靠依据,具有重要的临床意义。

Objective To study the diagnostic value of single nucleotide polymorphism(SNP)microarray and new generation gene capture sequencing technology in children with intellectual disabilities or mental retardation.Methods A total of 19 children with intellectual disabilities or mental retardation who were treated in the rehabilitation clinic of the Children’s Hospital Affiliated to Nanjing Medical University from September 2018 to March 2020 were selected by data analysis,including 11 boys and 8 girls aged from 6 months to 14-year-old.The developmental diagnosis scale and Wechsler intelligence scale for children revised in China(WISC-RC)were used to evaluate their intelligence.Those with a developmental quotient of less than 49 or an IQ of less than 51 were included in this study.The genome-wide copy number variation(CNV)and pathogenic gene variation were analyzed.The detected CNV was verified by proband and parents by quantitative PCR.The identified or suspected pathogenic gene variation was verified by dideoxy sequencing and family gene spectrum verification.Results The results of the study showed that 16 of the 19 selected children were negative in the SNP microarray analysis,which 6 cases were confirmed to have a single genetic disease,7 cases were negative,and 3 cases were suspectedgenetic lesions(manifested in 11q24.1q25,21q22.2q22.3,12q22.1q23,which were the main cause of mental retardation and intellectual disabilities).Conclusion The combined application of SNP microarray and a new generation gene capture sequencing technology can significantly improve the probability of molecular genetic etiology diagnosis of children with unexplained intellectual disabilities or mental retardation.The way of root searching and source searching can also provide a reliable basis for the direction of follow-up diagnosis and treatment,which has important clinical significance.