No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins.
John D. Murdoch,Abha R. Gupta,Stephen Sanders,Stephen Sanders,Michael F. Walker,John F. Keaney,Thomas V. Fernandez,Michael T. Murtha,Samuel Anyanwu,Gordon T. Ober,Melanie J. Raubeson,Nicholas M. DiLullo,Natalie M. Villa,Zainabdul Waqar,Catherine Sullivan,Luis Gonzalez,A. Jeremy Willsey,A. Jeremy Willsey,So-Yeon Choe,Benjamin M. Neale,Benjamin M. Neale,Mark J. Daly,Mark J. Daly,Matthew W. State,Matthew W. State +24 more
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TLDR
Target next-generation sequencing of contactin-Associated Proteins and related gene families finds no evidence for statistically significant association of rare heterozygous mutations in any of the CNTn or CNTNAP genes, including C NTNAP2, placing marked limits on the scale of their plausible contribution to risk.Abstract:
Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.read more
Citations
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Autism spectrum disorder
Catherine Lord,Traolach S. Brugha,Tony Charman,James C. Cusack,Guillaume Dumas,Thomas W. Frazier,Emily J.H. Jones,Rebecca M. Jones,Andrew Pickles,Matthew W. State,Julie Lounds Taylor,Jeremy Veenstra-VanderWeele +11 more
TL;DR: This Primer by Lord and colleagues reviews the epidemiology, mechanisms, clinical detection and treatment of autism and identifies the long-term needs of people with autism.
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Gene hunting in autism spectrum disorder: on the path to precision medicine
TL;DR: In this article, a convergent pathway for converging pathophysiology in autism spectrum disorder has been proposed, but how this notion of convergent pathways will translate into therapeutics remains to be established.
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Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context.
Adam J. Guastella,Ian B. Hickie +1 more
TL;DR: The potential of oxytocin-based therapies for social impairments in autism is explored and a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation is discussed.
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Behavioral phenotypes of genetic mouse models of autism
TL;DR: Robust, replicated autism‐relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism.
Journal ArticleDOI
Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications.
TL;DR: The objectives of this article are to review the current status of genetic research in ASD, and to provide information regarding the potential candidate genes, mutations, and genetic loci possibly related to pathogenesis in ASD.
References
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