Prevalence of four Mendelian disorders associated with autism in 2392 affected families

Abstract

Autism spectrum disorder (ASD) is a neurobehavioral disorder with a heterogeneous genetic etiology. Based on the literature, several single-gene disorders, including Rett syndrome, Smith-Lemli-Opitz syndrome, PTEN hamartoma tumor syndrome and tuberous sclerosis, are associated with a high prevalence of ASD. We estimated the prevalence of these four conditions in a large cohort of patients using whole-exome sequencing data from 2392 families (1800 quads and 592 trios) with ASD from the National Database for Autism Research. Seven patients carried a pathogenic or likely pathogenic variant in either TSC1, TSC2, PTEN, DHCR7 or MECP2, with 6 out of 7 reportable variants occurring in PTEN (1 in 399).