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

Abstract

To explore the genetic basis for a child with mental retardation. 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. 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). The child had XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I due to biallelic pathogenic variants of the AUH gene.