title: 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).
authors.affiliation: Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Avi
authors.initials: A
authors.lastname: Saskin
authors.affiliation: Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fulginiti
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ashley H
authors.initials: AH
authors.lastname: Birch
authors.affiliation: Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Trakadis
mesh_terms: D000067877:Autism Spectrum Disorder / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D015518:Rett Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics* / Q000473:pathology; D014402:Tuberous Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000073359:Exome Sequencing / Q000379:methods
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human