目的 调查安徽省120例智力障碍(ID)／发育迟缓(DD)儿童致病性与可能致病性拷贝数变异(CNVs)的检出情况,并分析患儿临床表型,明确ID／DD患儿遗传学病因,为患儿的治疗及其父母再生育指导提供依据。方法 选取2019年5月—2020年6月在安徽省儿童医院小儿康复科就诊的120例不明原因ID／DD患儿,行染色体微阵列分析(CMA)检测明确存在的致病性与可能致病性CNVs,分析患儿临床表型及致病性与可能致病性CNVs特点。结果 120例ID／DD患儿检出致病性CNVs 18例(15.00%),可能致病性CNVs 2例(1.67%),意义不明的CNVs 39例(32.50%),可能良性和良性CNVs 61例(50.83%)。20例检出致病性与可能致病性CNVs的患儿伴先天畸形／特殊面容5例,伴1种或多种其他疾病14例;轻、中、重度智力低下分别为3、12、5例。20例ID／DD患儿共存在21处致病性或可能致病性CNVs,其中微缺失片段13个(占61.90%),微重复片段8个(占38.10%),比例约为1.63∶1,片段平均大小6.34 Mb。21处致病性与可能致病性CNVs以2号与22号染色体(3处)检出最多。20例ID／DD患儿中,已知综合征10例(50.00%),仍有10例(50.00%)为数据库中暂未定义的综合征或疾病区域。结论 对于不明原因ID／DD患儿,应用CMA方法进行检测可明确其遗传学病因,对患儿的治疗及其父母再生育指导意义重大。
Abstract
Objective To investigate the detection of pathogenic and likely pathogenic copy number variations (CNVs) in 120 children with intellectual disability (ID)/developmental delay (DD) in Anhui province, and to analyze the clinical phenotype of the children, so as to clarify the genetic etiology of ID/DD children. Methods A total of 120 children with unexplained ID/DD who were treated in the Department of Pediatric Rehabilitation of Anhui Children′s Hospital from May 2019 to June 2020 were selected and tested for the presence of pathogenic and likely pathogenic CNVs by chromosome microarray analysis (CMA).The clinical phenotype and characteristics of pathogenic and likely pathogenic CNVs were analyzed. Results Among 120 children with ID/DD, pathogenic CNVs were detected in 18 cases (15.00%), likely pathogenic CNVs in 2 cases (1.67%), variation of uncertain significance CNVs in 39 cases (32.50%), and likely benign and benign CNVs in 61 cases (50.83%). Among 20 children with pathogenic and likely pathogenic CNVs, 5 had congenital malformations/special faces, and 14 had one or more other diseases. There were 3 cases, 12 cases and 5 cases with mild, moderate and severe mental retardation, respectively. There were 21 pathogenic and likely pathogenic CNVs in 20 children with ID/DD, including 13 microdeletion fragments (61.90%) and 8 microduplication fragments (38.10%) with a ratio of 1.63∶1. The average fragment size was 6.34 Mb. Twenty one pathogenic and possibly pathogenic CNVs were detected most on chromosomes 2 and 22 (3 locations).Among the 20 children with ID/DD, 10 cases (50.00%) had known syndromes, and 10 cases (50.00%) had still undefined syndromes or disease areas in the database. Conclusion For children with unexplained ID/DD, CMA detection can clarify the genetic etiology, which is of great significance for the treatment of children and guidance for their parents to reproduce.
关键词
智力障碍 /
发育迟缓 /
染色体微阵列分析 /
拷贝数变异 /
临床表型
Key words
intellectual disability /
developmental delay /
chromosome microarray analysis /
copy number variation /
clinical phenotype
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基金
安徽省科技厅重点研究与开发计划项目A类(1804h08020254)
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