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

Publication ,  Journal Article
Noor, A; Whibley, A; Marshall, CR; Gianakopoulos, PJ; Piton, A; Carson, AR; Orlic-Milacic, M; Lionel, AC; Sato, D; Pinto, D; Drmic, I; Mo, R ...
Published in: Sci Transl Med
September 15, 2010

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.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 15, 2010

Volume

2

Issue

49

Start / End Page

49ra68

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Potassium Channels
  • Oligonucleotide Array Sequence Analysis
  • Nerve Tissue Proteins
  • Mutation
  • Mice
  • Membrane Proteins
  • Male
  • Intellectual Disability
  • In Situ Hybridization
 

Citation

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Noor, A., Whibley, A., Marshall, C. R., Gianakopoulos, P. J., Piton, A., Carson, A. R., … Vincent, J. B. (2010). Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. Sci Transl Med, 2(49), 49ra68. https://doi.org/10.1126/scitranslmed.3001267
Noor, Abdul, Annabel Whibley, Christian R. Marshall, Peter J. Gianakopoulos, Amelie Piton, Andrew R. Carson, Marija Orlic-Milacic, et al. “Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability.Sci Transl Med 2, no. 49 (September 15, 2010): 49ra68. https://doi.org/10.1126/scitranslmed.3001267.
Noor A, Whibley A, Marshall CR, Gianakopoulos PJ, Piton A, Carson AR, et al. Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. Sci Transl Med. 2010 Sep 15;2(49):49ra68.
Noor, Abdul, et al. “Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability.Sci Transl Med, vol. 2, no. 49, Sept. 2010, p. 49ra68. Pubmed, doi:10.1126/scitranslmed.3001267.
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. Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. Sci Transl Med. 2010 Sep 15;2(49):49ra68.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 15, 2010

Volume

2

Issue

49

Start / End Page

49ra68

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Potassium Channels
  • Oligonucleotide Array Sequence Analysis
  • Nerve Tissue Proteins
  • Mutation
  • Mice
  • Membrane Proteins
  • Male
  • Intellectual Disability
  • In Situ Hybridization