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Neurofibromatosis Type 1 Implicates Ras Pathways in the Genetic Architecture of Neurodevelopmental Disorders

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Abstract

The genetic architecture of neurodevelopmental disorders is largely polygenic, non-specific, and pleiotropic. This complex genetic architecture makes the search for specific etiological mechanisms that contribute to neurodevelopmental risk more challenging. Monogenic disorders provide an opportunity to focus in on how well-articulated signaling pathways contribute to risk for neurodevelopmental outcomes. This paper will focus on neurofibromatosis type 1 (NF1), a rare monogenic disorder that is associated with varied neurodevelopmental outcomes. Specifically, this paper will provide a brief overview of NF1 and its phenotypic associations with autism spectrum disorder, attention-deficit/hyperactivity disorder, and specific learning disorders, describe how variation within the NF1 gene increases risk for neurodevelopmental disorders via altered Ras signaling, and provide future directions for NF1 research to help elucidate the genetic architecture of neurodevelopmental disorders in the general population.

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Acknowledgements

The authors would like to thank Jean Davidson for creating Figure 1.

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Authors and Affiliations

  1. Department of Psychology and Child Development, California Polytechnic State University, San Luis Obispo, 1 Grand Ave, San Luis Obispo, CA, 93407-0387, USA

    Jessica A. Kaczorowski, Taylor F. Smith, Amanda M. Shrewsbury & Leah R. Thomas

  2. Department of Human Development and Family Studies, Purdue University, West Lafayette, IN, USA

    Valerie S. Knopik

  3. Office of the Clinical Director and Medical Genetic Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA

    Maria T. Acosta

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  1. Jessica A. Kaczorowski
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  2. Taylor F. Smith
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Correspondence to Jessica A. Kaczorowski.

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Jessica A. Kaczorowski, Taylor F. Smith, Amanda M. Shrewsbury, Leah R. Thomas, Valerie S. Knopik and Maria T. Acosta declare that they have no confict of interest.

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Kaczorowski, J.A., Smith, T.F., Shrewsbury, A.M. et al. Neurofibromatosis Type 1 Implicates Ras Pathways in the Genetic Architecture of Neurodevelopmental Disorders. Behav Genet 50, 191–202 (2020). https://doi.org/10.1007/s10519-020-09991-x

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