Abstract: Objective To seek related genetic pathogenic factors by screening for genome-wide copy number variations (CNVs) in 55 Chinese children with unexplained mental retardation or developmental delay (MR/DD) using high resolution array-comparative genomic hybridization (aCGH), identify rare CNVs (microdeletions/duplications) which may associate with MR/DD, and evaluate the effectiveness of aCGH in clinical molecular diagnosis of children with unexplained MR/DD. Methods A total of 55 children with unexplained MR/DD were recruited for this study from June to December in 2013 in SUN Yat-sen Memorial Hospital.Their genomic CNVs were detected by using 25~50 K CytoScan HD chip, then the pathogenic CNVs were analyzed with bioinformatics tools. Results Rare CNVs were identified on 21 out of 55 children with unexplained MR/DD, which had been analyzed with the references from database of genomic variants and were considered as pathogenic CNVs.19 CNVs were related to MR/DD while the other 2 were associated with known syndromes. Conclusions Microdeletions/microduplications related to the genomic CNVs, which couldn't be identified using traditional chromosome analysis, are demonstrated as one of the cause of unexplained MR/DD.aCGH could help with the clinical molecular diagnosis and prognosis of children with unexplained MR/DD, and with the evaluation of the risk of family-recurrence.

Key words: array-comparative genomic hybridization, mental retardation, developmental delay, copy number variations

摘要： 目的 应用高分辨微阵列比较基因组杂交技术(array-comparative genomic hybridization, aCGH)对55例不明原因的智力低下或发育迟缓(mental retardation or developmental delay, MR/DD)患儿进行拷贝数变异(copy number variations, CNVs)检测, 寻求与遗传学相关的致病因素, 探讨aCGH对不明原因MR/DD患儿可能的分子病因诊断的作用。方法 收集2013年6月-2013 年12月到本院儿科初步诊断为MR/DD的患儿55例, 应用25~50 K CytoScan HD芯片检测全基因组CNVs, 联合生物信息学分析手段分析致病性CNVs。结果 在55例不明原因MR/DD患者中共检测到21例存在罕见CNVs。通过比对数据库, 21处CNVs确认为致病性CNVs。19例患者携带与MR/DD相关的CNVs。2例为已知综合征患者, 其中1例为Turner综合征, 1例为1p36缺失综合征。结论 基因组CNVs相关的微缺失或微重复是不明原因MR/DD的病因之一, 这些片段均无法被常规染色体G带检查所识别。aCGH可以提高对不明原因MR/DD患儿的分子病因诊断水平, 对深入研究MR/DD病因机制有重要意义, 为患儿预后和家庭再发风险评估提供指导。

关键词: 微阵列比较基因组杂交技术, 智力低下, 发育迟缓, 拷贝数变异