PT  - JOURNAL ARTICLE
AU  - Andreas Buja
AU  - Natalia Volfovsky
AU  - Abba Krieger
AU  - Catherine Lord
AU  - Alex E. Lash
AU  - Michael Wigler
AU  - Ivan Iossifov
TI  - Damaging Mutations are Associated with Diminished Motor Skills and IQ in Children on the Autism Spectrum
AID  - 10.1101/141200
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 141200
4099  - http://biorxiv.org/content/early/2017/05/23/141200.short
4100  - http://biorxiv.org/content/early/2017/05/23/141200.full
AB  - 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, as judged by the type and its gene target. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of both), moderate (impairment mainly to motor skills) and severe (impairment of both).