Objective: To investigate the association between genotype and phenotype of microdeletion and microduplication syndromes (MMSs) and the pathogenesis of pathogenic copy number variations (CNVs).
Methods: A total of 50 children with MMSs diagnosed by chromosomal microarray analysis (CMA) from June 2013 to September 2015 were enrolled, and the clinical manifestations and features of pathogenic CNVs were analyzed.
Results: The main clinical manifestations of children with MMSs included mental retardation, developmental delay, short stature, and unusual facies, with the presence of abnormalities in multiple systems. There were 54 pathogenic CNVs in total, consisting of 36 microdeletion segments and 18 microduplication segments, with sizes ranging from 28 kb to 48.5 Mb (mean 13.86 Mb). Pathogenic CNVs often occurred in chromosomes X, 15, and 1.
Conclusions: The clinical manifestations of MMSs are not specific, and a genotype-first approach can be used for diagnosis. Mode of inheritance, type of recombination (deletion or duplication), size of segment, and functional genes included helps with the interpretation of CNVs of de novo mutations, and in-depth research on rare pathogenesis may become breakthrough points for the identification of new MMSs.
目的: 了解微缺失和微重复综合征（MMSs）的基因型与临床表型的关系及致病性拷贝数变异（CNVs）的发生机制。
方法: 收集2013年6月至2015年9月，应用染色体微阵列（CMA）诊断为MMSs的患儿50例，总结分析其临床表现和致病性CNVs的特点。
结果: 50例MMSs患儿临床表现以精神发育迟滞（MR）、发育迟缓（DD）、矮小、特殊面容为主，且往往多系统的异常同时存在，共存在54处致病性CNVs，微缺失片段36个、微重复片段18个，片段大小介于28 kb至48.5 Mb，平均13.86 Mb。致病性CNVs易发生在X染色体、15号染色体、1号染色体。
结论: MMSs临床表现缺乏特异性，可以采取基因型优先的方法进行诊断。遗传方式、重组类型（缺失或者重复）、片段大小以及所包含的功能基因有利于新生突变CNVs的解读，少见发病机制的深入研究有望成为发现新的罕见MMSs的突破点。