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Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder

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Abstract

Approximately one-third of children with autism spectrum disorder (ASD) reportedly lose skills within the first 3 years, yet a causal mechanism remains elusive. Considering evidence of strong genetic effects for ASD and findings that distinct phenotypes in ASD associate with specific genetic events, we examined rates of parent-reported regression in the Simons Simplex Collection with likely gene disrupting mutations from five distinct classes: FMRP target genes, genes encoding chromatin modifiers, genes expressed preferentially in embryos, genes encoding postsynaptic density proteins, and essential genes. Children with ASD and mutations in postsynaptic density genes were more likely to experience regression, while a trend suggested that children with ASD and mutations in embryonic genes were less likely to have skill losses.

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Acknowledgments

We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, (A) Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, (B) Peterson, J. Piggot, (C) Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the SSC population dataset described in this study by applying at https://base.sfari.org.

Funding

Funding for this study was provided by the National Institutes for Mental Health (#R01MH100047 to R.B.) and by the Simons Foundation (SSC-15 to R.G.K. and SFARI #89368 to R.B.).

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Author notes

  1. Robin P. Goin-Kochel and Raphael Bernier have contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA

    Robin P. Goin-Kochel

  2. Autism Center, Texas Children’s Hospital, Houston, TX, USA

    Robin P. Goin-Kochel

  3. Department of School Psychology, University of Washington, Seattle, Washington, USA

    Sandy Trinh & Shelley Barber

  4. Department of Psychiatry, University of Washington, Seattle, Washington, USA

    Raphael Bernier

  5. Center on Human Development and Disability, University of Washington, Seattle, WA, USA

    Raphael Bernier

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  1. Robin P. Goin-Kochel
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  2. Sandy Trinh
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  3. Shelley Barber
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  4. Raphael Bernier
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Contributions

RPG-K conceived of the study, participated in its design and coordination, interpretation of the data, and drafted the manuscript; ST participated in the interpretation of the data and helped to draft the manuscript; SB participated in the interpretation of the data and helped to draft the manuscript; RB conceived of the study, participated in its design and coordination, interpretation of the data, and drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Robin P. Goin-Kochel or Raphael Bernier.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the current study through their initial participation in the Simons Simplex Collection.

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Goin-Kochel, R.P., Trinh, S., Barber, S. et al. Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder. J Autism Dev Disord 47, 3600–3607 (2017). https://doi.org/10.1007/s10803-017-3256-4

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