Journal
MOLECULAR PSYCHIATRY
Volume 22, Issue 4, Pages 625-633Publisher
SPRINGERNATURE
DOI: 10.1038/mp.2016.61
Keywords
-
Funding
- Institut Pasteur
- Bettencourt-Schueller Foundation
- Centre National de la Recherche Scientifique
- University Paris Diderot
- Agence Nationale de la Recherche [ANR-08-MNPS-037-01- SynGen]
- Conny-Maeva Charitable Foundation
- Cognacq Jay Foundation
- Orange Foundation
- Fondamental Foundation
- GenMed Labex
- BioPsy labex
- Neuropole de Recherche Francilien (NeRF)
- Innovative Medicines Initiative Joint Undertaking [115300]
- European Union
- Division of Aging Biology, National Institute on Aging
- Division of Geriatrics and Clinical Gerontology, National Institute on Aging
Ask authors/readers for more resources
Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P = 0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P = 0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6(W923X) was transmitted by a mother to her two sons with ASD and one variant CNTN6(P770L) was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.
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