摘要目的 应用高分辨微阵列比较基因组杂交(Array-CGH)技术对不明原因的精神发育迟滞/迟缓(MR/DD)患儿进行染色体微失衡的检测,获得这些不明病因MR/DD患儿中染色体微失衡的检出率,评估Array-CGH技术对不明病因MR/DD的病因诊断作用,实现MR/DD的病因学诊断.方法 根据特定条件筛选不明原因的MR/DD患儿126例,应用Array-CGH技术对染色体微失衡进行筛查.针对发现的染色体微失衡,通过比对国际基因组拷贝数异常多态性数据库排除良性染色体微失衡,结合基因组异常拷贝数变异数据库与相关文献,判断染色体微失衡的临床意义.结果 通过评估,在126例不明原因的MR/DD患儿,26例检出28个与临床MR/DD相关的染色体微失衡,检出率为20.6％(26/126例).这些染色体微失衡均无法被常规染色体G带检测所识别.阳性患儿均伴有异常面容和/或体表、内脏畸形.其中Prader-Willi综合征/Angelman综合征比例最高(3/26例,11.5％),其次为DiGeroge综合征(2/26例,7.6％)、猫叫综合征(2/26例,7.6％)及16p11.2缺失综合征(2/26例,7.6％).结论 染色体微失衡是MR/DD患儿的病因之一,Array-CGH技术可以实现染色体微失衡的诊断.对于MR/DD同时伴有异常面容和/或体表、内脏畸形的患儿应首先选择染色体微失衡的检测.

abstractsObjective To investigate clinically chromosome micro imbalance in children with unexplained mental retardation(MR) or development delay(DD) by using high resolution microarray comparative genomic hybridization(Array-CGH),to identify chromosome micro imbalance which might be associated with MR/DD,and evaluate the effectiveness of Array-CGH in etiological diagnosis of children with unexplained MR/DD.Methods One hundred and twenty-six children with unexplained MR/DD were recruited for this study by Array-CGH to detect chromosome micro imbalance.All chromosome micro imbalances were verified with database of genomic variation(DGV),Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources(DECIPHER) and literature review,to determine if the chromosome micro imbalances found in these children were associated with MR/DD.Results Twenty eight clinically relevant chromosome micro imbalances were detected among 26 children out of 126 children with unexplained MR/DD.The diagnostic yield for the MR/DD children was 20.6％ (26/126 cases).These chromosome micro imbalances were undetectable by chromosome analysis.All MR/DD children with chromosome micro imbalances had face dysmorphism and/or surface,organ dysmorphism.The most common abnormality was Prader-Willi syndrome/Angelman syndrome(3/26 cases,11.5％),which was followed by DiGeroge syndrome(2/26 cases,7.6％),Cri-du chat syndrome(2/26 cases,7.6％) and 16p11.2 deletion syndrome(2/26 cases,7.6％).Conclusions Chromosome micro imbalance is one of the most common causes of unexplained MR/DD.Array-CGH can detect disease associated with chromosome micro imbalance as a useful evaluation to help differential diagnosis of children with unexplained MR/DD.Screening for chromosome micro imbalance should be firstly carried out in those MR/DD children with face dysmorphism and/or surface,organ dysmorphism.