摘要目的:对一例智力落后的患儿及其家系进行遗传学分析。方法:对患儿进行染色体微阵列分析(chromosomal microarray analysis，CMA)以及遗传代谢病相关基因进行高通量测序，对候选变异进行Sanger测序验证。结果:CMA提示患儿为47，XYY；高通测序发现患儿 AUH基因存在c.677G>A(p.R226H)和c.373C>T(p.R125W)复合杂合变异，分别遗传自父母，根据美国医学遗传学以及基因组学学会的分类标准，c.677G>A(p.R226H)变异判定为临床意义不明(PM2+PP4+PP3)，c.373C>T(p.R125W)变异为可能致病(PM1+PM2+PP3+PP4)。 结论:患儿患有XYY综合征，合并由 AUH基因复合杂合变异导致的3-甲基戊烯二酸尿症I型(3-methylglutaconic aciduria type I)。

abstractsObjective:To explore the genetic basis for a child with mental retardation.Methods:The child was subjected to chromosomal microarray analysis (CMA) and targeted capture next-generation sequencing for the exons of genes related to genetic and metabolic diseases. Candidate variants were verified by Sanger sequencing of the child and his parents.Results:CMA suggested that the child has a 47, XYY karyotype. Next-generation sequencing revealed that the child has harbored compound heterozygous variants of the AUH gene, including c. 677G>A (p.R226H) and c. 373C>T (p.R125W), which were respectively inherited from his parents. Based on the American college of Medical Genetics and Genomics (ACMG) standards and guidelines, the c. 677G>A (P.r226h) variant was predicted as variant of uncertain significance (PM2+ PP4+ PP3), whilst the c. 373C>T (P.R125W) variant was predicted as likely pathogenic (PM1+ PM2+ PP3+ PP4). Conclusion:The child had XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I due to biallelic pathogenic variants of the AUH gene.