CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

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.Molecular Psychiatry advance online publication, 10 May 2016; doi:10.1038/mp.2016.61.

Huguet, GPasteur Institute (author)
Danckaert, APasteur Institute (author)
André-Leroux, GPasteur Institute (author)
Maruani, A (author)
Bellinzoni, M (author)
Rolland, T (author)
Gouder, L (author)
Mathieu, A (author)
Buratti, J (author)
Amsellem, F (author)
Benabou, M (author)
Van-Gils, J (author)
Beggiato, A (author)
Konyukh, M (author)
Bourgeois, J-P (author)
Gazzellone, M J (author)
Yuen, R K C (author)
Walker, S (author)
Delépine, M (author)
Boland, A (author)
Régnault, B (author)
Francois, M (author)
Van Den Abbeele, T (author)
Mosca-Boidron, A L (author)
Faivre, L (author)
Shimoda, Y (author)
Watanabe, K (author)
Bonneau, D (author)
Råstam, Maria,1948Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Gillbergcentrum,Gillberg Neuropsychiatry Centre,Barn- och ungdomspsykiatri,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Child and Adolescent Psychiatry,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-mr_ (author)
Leboyer, M (author)
Scherer, S W (author)
Gillberg, Christopher,1950University of Gothenburg,Gothenburg University,Göteborgs universitet,Gillbergcentrum,Gillberg Neuropsychiatry Centre(Swepub:gu)xgilch (author)
Delorme, R (author)
Cloëz-Tayarani, I (author)
Bourgeron, ThomasGothenburg University,Göteborgs universitet,Gillbergcentrum,Gillberg Neuropsychiatry Centre,Pasteur Institute(Swepub:gu)xbouth (author)
Pasteur InstituteGillbergcentrum (creator_code:org_t)

In:Molecular psychiatry: Springer Science and Business Media LLC22, s. 625-6331476-55781359-4184

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Psychiatry

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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