Research ArticleAutism Spectrum Disorder

Disruption at the PTCHD1 Locus on Xp22.11 in Autism Spectrum Disorder and Intellectual Disability

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Science Translational Medicine  15 Sep 2010:
Vol. 2, Issue 49, pp. 49ra68
DOI: 10.1126/scitranslmed.3001267

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A Patch in the Fabric of Autism

What causes autism? This disabling disorder is characterized by severe language and social impairment and is now included under the umbrella term “autism spectrum disorder” (ASD), which also includes milder deficits in communication and social development. Numerous theories have been advanced as to its causes. These have ranged from discredited concepts—“refrigerator” mothers and vaccines—to the modern idea of gene-environment interactions. Although no one gene simply explains the predisposition of patients for ASD, these disorders are wellknown to have a strong genetic component. Here, Noor et al. report the results of genetic analysis in thousands of patients and control subjects: Mutations at the PTCHD1 (patched-related gene) locus are associated with the inheritance of ASD and with intellectual disability in a small fraction of cases.

In this study, the authors analyzed the PTCHD1 gene from 1896 patients with ASD and 246 with intellectual disability, and compared these to more than 10,000 control individuals, and found mutations in various parts of this gene in 25 affected individuals in 20 different families, but not in any of the controls. Some patients had large deletions, in one case spanning the entire gene, and in others the culprit was a missense mutation. A result of this gene’s location on the X chromosome, the affected patients were almost all male, and most had unaffected mothers and other female relatives. The authors also present evidence that the PTCHD1 gene may be part of the Hedgehog signaling pathway, which is important in embryonic development.

Autism and intellectual disability are not straightforward disorders that can be attributed to mutations in a single gene. Even when candidate genes such as PTCHD1 are known, differences in the gene sequence do not perfectly correlate with phenotype, because there are many as yet undefined additional genes and environmental influences that dictate the ultimate characteristics of the person. Identifying some of these genes, as Noor et al. have done in this study, allows a better understanding of the disorder and the development of ways to compensate for its disabilities.


  • * Present address: CNRS/Museum National d’Histoire Naturelle, Paris 75005, France.

  • See supplementary material for full list of names and affiliations.

  • Citation: A. Noor, A.Whibley, C. R.Marshall, P. J. Gianakopoulos, A. Piton, A. R. Carson, M. Orlic-Milacic, A. Lionel, D. Sato, D. Pinto, I. Drmic, C. Noakes, L. Senman, X. Zhang, R. Mo, J. Gauthier, J. Crosbie, A. T. Pagnamenta, J. Munson, A. M. Estes, A. Fiebig, A. Franke, S. Schreiber, A. F. R. Stewart, R. Roberts, R. McPherson, S. J. Guter, E. H. Cook Jr., G. Dawson, G. D. Schellenberg, A. Battaglia, E. Maestrini, Autism Genome Project Consortium, L. Jeng, T.Hutchison, E. Rajcan-Separovic, A. E. Chudley, S. M. E. Lewis, X. Liu, J. Holden, B. Fernandez, L. Zwaigenbaum, S. E. Bryson, W. Roberts, P. Szatmari, L. Gallagher, M. R. Stratton, J. Gecz, A. F. Brady, C. E. Schwartz, R. J. Schachar, A. P.Monaco, G. A. Rouleau, C. Hui, F. L. Raymond, S. W. Scherer, J. B. Vincent, Disruption at the PTCHD1 locus on Xp22.11 in autism spectrum disorder and intellectual disability. Sci. Transl. Med. 2, 49ra68 (2010).

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