一例XYY综合征合并3-甲基戊烯二酸尿症I型患儿的遗传学分析

Genetic analysis of a child with XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I

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)。

Objective 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.