Damaging de novo mutations diminish motor skills in children on the autism spectrum

Buja, A., Volfovsky, N., Krieger, A. M., Lord, C., Lash, A. E., Wigler, M., Iossifov, I. (February 2018) Damaging de novo mutations diminish motor skills in children on the autism spectrum. Proc Natl Acad Sci U S A, 115 (8). E1859-E1866. ISSN 0027-8424

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URL: https://www.ncbi.nlm.nih.gov/pubmed/29434036
DOI: 10.1073/pnas.1715427115

Abstract

In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills).

Item Type: Paper
Uncontrolled Keywords: Iq autism de novo mutation genetics motor skills
Subjects: diseases & disorders > mental disorders > personality disorders > autism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > de novo mutation
CSHL Authors:
Communities: CSHL labs > Iossifov lab
CSHL labs > Wigler lab
Depositing User: Matt Covey
Date: 20 February 2018
Date Deposited: 21 Feb 2018 14:36
Last Modified: 07 Mar 2018 13:49
PMCID: PMC5828599
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36072

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