一例21号染色体三体嵌合型孤独症谱系障碍患儿的遗传学分析

目的对1例孤独症谱系障碍(autism spectrum disorder,ASD)伴有先天性心脏病的患儿进行细胞遗传学和分子遗传学分析,寻找其病因。方法取患儿及其父母的外周血进行常规染色体G显带核型分析,对患儿外周血提取的基因组DNA进行基于高通量测序的全外显子测序(whole exome sequencing,WES)和低覆盖度全基因组拷贝数变异测序(low-coverage massively parallel copy number variation sequencing,CNV-seq)检测分析,并利用染色体微阵列分析(chromosomal microarray analysis,CMA)进行验证。结果常规染色体G显带核型分析结果显示患儿及其父母染色体核型正常,患儿WES未检测到异常变异,而CNV-seq检测结果为47,XY,+2110%]/46,XY90%],提示存在低比例的21号染色体三体嵌合,CMA验证结果与CNV-seq结果一致。结论低比例的21号染色体三体嵌合除与唐氏综合征表型有关外,还可能与ASD的发生密切相关。基于高通量测序的WES及CNV-seq方法可为原因不明的ASD提供准确的遗传学诊断。

Genetic analysis of a case of mosaic trisomy 21 associated with autism spectrum disorder

Objective To explore the genetic basis for a child with autism spectrum disorder(ASD)and congenital heart disease.Methods G-banded chromosomal karyotyping was carried out for the patient and his parents.The child was also subjected to whole exome sequencing(WES)and low-coverage massively parallel copy number variation sequencing(CNV-seq).The result was validated by chromosomal microarray analysis(CMA).Results The karyotype of the patient and his parents were normal.No significant genetic variation was found by WES.However,CNV-seq has discovered a 47,XY,+2110%]/46,XY90%]mosaicism in the patient.The result was confirmed by CMA.Conclusion In addition to Down syndrome,low proportion mosaic trisomy 21 is also associated with ASD.WES and CNV-seq can enable accurate diagnosis for patient with unexplained ASD.