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

Mercati, O ; Huguet, G; Danckaert, A; André-Leroux, G; Maruani, A; Bellinzoni, M; Rolland, T; Gouder, L; Mathieu, A and Buratti, J, et al. (2016) In Molecular Psychiatry
Abstract
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... (More)
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 CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L 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. (Less)
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Molecular Psychiatry
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9 pages
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Nature Publishing Group
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  • scopus:84966656940
ISSN
1359-4184
DOI
10.1038/mp.2016.61
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English
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7bb229de-0d6d-49a7-b570-5d91a4dd4307
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2016-07-05 11:35:24
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2017-03-21 03:02:47
@article{7bb229de-0d6d-49a7-b570-5d91a4dd4307,
  abstract     = {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<br/>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 CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L 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. },
  author       = {Mercati, O  and Huguet, G and Danckaert, A and André-Leroux, G and Maruani, A and Bellinzoni, M and Rolland, T and Gouder, L and Mathieu, A and Buratti, J and Amsellem, F and Benabou, M and Van-Gils, J and Beggiato, A and Konyukh, M and Bourgeois, J-P and Gazzellone, M J and Yuen, R K C and Walker, S and Delépine, M and Boland, A and Régnault, B and Francois, M and Van Den Abbeele, T and Mosca-Boidron, A L and Faivre, L and Shimoda, Y and Watanabe, K and Bonneau, D and Råstam, Maria and Leboyer, M and Scherer, S W and Gillberg, C and Delorme, R and Cloëz-Tayarani, I and Bourgeron, T},
  issn         = {1359-4184},
  language     = {eng},
  month        = {05},
  pages        = {9},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Psychiatry},
  title        = {CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders},
  url          = {http://dx.doi.org/10.1038/mp.2016.61},
  year         = {2016},
}