Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Volume 183, Issue 6, Pages 341-351Publisher
WILEY
DOI: 10.1002/ajmg.b.32806
Keywords
autism; autism spectrum disorder; CAG tract; huntingtin; Huntington's disease
Categories
Funding
- EU Innovative Medicines Initiative Joint Undertaking [115300]
- European Commission H2020 Project Joint Programme - Neurodegenerative Disease Research (JPND) ModelPolyQ [643417]
- Italian Ministry of Health [NET-2013-02355263, CCR-2017-9999901]
Ask authors/readers for more resources
The Huntingtin (HTT) gene contains a CAG repeat in exon 1, whose expansion beyond 39 repeats consistently leads to Huntington's disease (HD), whereas normal-to-intermediate alleles seemingly modulate brain structure, function and behavior. The role of the CAG repeat in Autism Spectrum Disorder (ASD) was investigated applying both family-based and case-control association designs, with the SCA3 repeat as a negative control. Significant overtransmission of long CAG alleles (>= 17 repeats) to autistic children and of short alleles (<= 16 repeats) to their unaffected siblings (allp < 10(-5)) was observed in 612 ASD families (548 simplex and 64 multiplex). Surprisingly, both 193 population controls and 1,188 neurological non-HD controls have significantly lower frequencies of short CAG alleles compared to 185 unaffected siblings and higher rates of long alleles compared to 548 ASD patients from the same families (p < .05-.001). The SCA3 CAG repeat displays no association. Short HTT alleles seemingly exert a protective effect from clinically overt autism in families carrying a genetic predisposition for ASD, while long alleles may enhance autism risk. Differential penetrance of autism-inducing genetic/epigenetic variants may imply atypical developmental trajectories linked to HTT functions, including excitation/inhibition imbalance, cortical neurogenesis and apoptosis, neuronal migration, synapse formation, connectivity and homeostasis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available