Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability.

Journal Article (Journal Article)

Autism is a common neurodevelopmental disorder with a complex mode of inheritance. It is one of the most highly heritable of the complex disorders, although the underlying genetic factors remain largely unknown. Here, we report mutations in the X-chromosome PTCHD1 (patched-related) gene in seven families with autism spectrum disorder (ASD) and in three families with intellectual disability. A 167-kilobase microdeletion spanning exon 1 was found in two brothers, one with ASD and the other with a learning disability and ASD features; a 90-kilobase microdeletion spanning the entire gene was found in three males with intellectual disability in a second family. In 900 probands with ASD and 208 male probands with intellectual disability, we identified seven different missense changes (in eight male probands) that were inherited from unaffected mothers and not found in controls. Two of the ASD individuals with missense changes also carried a de novo deletion at another ASD susceptibility locus (DPYD and DPP6), suggesting complex genetic contributions. In additional males with ASD, we identified deletions in the 5' flanking region of PTCHD1 that disrupted a complex noncoding RNA and potential regulatory elements; equivalent changes were not found in male control individuals. Thus, our systematic screen of PTCHD1 and its 5' flanking regions suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.

Full Text

Duke Authors

Cited Authors

  • Noor, A; Whibley, A; Marshall, CR; Gianakopoulos, PJ; Piton, A; Carson, AR; Orlic-Milacic, M; Lionel, AC; Sato, D; Pinto, D; Drmic, I; Noakes, C; Senman, L; Zhang, X; Mo, R; Gauthier, J; Crosbie, J; Pagnamenta, AT; Munson, J; Estes, AM; Fiebig, A; Franke, A; Schreiber, S; Stewart, AFR; Roberts, R; McPherson, R; Guter, SJ; Cook, EH; Dawson, G; Schellenberg, GD; Battaglia, A; Maestrini, E; Autism Genome Project Consortium, ; Jeng, L; Hutchison, T; Rajcan-Separovic, E; Chudley, AE; Lewis, SME; Liu, X; Holden, JJ; Fernandez, B; Zwaigenbaum, L; Bryson, SE; Roberts, W; Szatmari, P; Gallagher, L; Stratton, MR; Gecz, J; Brady, AF; Schwartz, CE; Schachar, RJ; Monaco, AP; Rouleau, GA; Hui, C-C; Lucy Raymond, F; Scherer, SW; Vincent, JB

Published Date

  • September 15, 2010

Published In

Volume / Issue

  • 2 / 49

Start / End Page

  • 49ra68 -

PubMed ID

  • 20844286

Pubmed Central ID

  • PMC2987731

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.3001267


  • eng

Conference Location

  • United States