Abstract
Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.
Original language | English (US) |
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Pages (from-to) | 399-414 |
Number of pages | 16 |
Journal | Behavior Genetics |
Volume | 49 |
Issue number | 4 |
DOIs | |
State | Published - Jul 15 2019 |
Keywords
- Autism spectrum disorder
- Childhood apraxia of speech
- Comorbidity
- Complex trait
- Heterogeneity
- Language impairment
- Multiple hits
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Genetics(clinical)