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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 a...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378808/ https://www.ncbi.nlm.nih.gov/pubmed/27166760 http://dx.doi.org/10.1038/mp.2016.61 |
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author | Mercati, O Huguet, G Danckaert, A André-Leroux, G Maruani, A Bellinzoni, M Rolland, T Gouder, L Mathieu, A Buratti, J Amsellem, F Benabou, M Van-Gils, J Beggiato, A Konyukh, M Bourgeois, J-P Gazzellone, M J Yuen, R K C Walker, S Delépine, M Boland, A Régnault, B Francois, M Van Den Abbeele, T Mosca-Boidron, A L Faivre, L Shimoda, Y Watanabe, K Bonneau, D Rastam, M Leboyer, M Scherer, S W Gillberg, C Delorme, R Cloëz-Tayarani, I Bourgeron, T |
author_facet | Mercati, O Huguet, G Danckaert, A André-Leroux, G Maruani, A Bellinzoni, M Rolland, T Gouder, L Mathieu, A Buratti, J Amsellem, F Benabou, M Van-Gils, J Beggiato, A Konyukh, M Bourgeois, J-P Gazzellone, M J Yuen, R K C Walker, S Delépine, M Boland, A Régnault, B Francois, M Van Den Abbeele, T Mosca-Boidron, A L Faivre, L Shimoda, Y Watanabe, K Bonneau, D Rastam, M Leboyer, M Scherer, S W Gillberg, C Delorme, R Cloëz-Tayarani, I Bourgeron, T |
author_sort | Mercati, O |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5378808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53788082017-04-27 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 Buratti, J Amsellem, F Benabou, M Van-Gils, J Beggiato, A Konyukh, M Bourgeois, J-P Gazzellone, M J Yuen, R K C Walker, S Delépine, M Boland, A Régnault, B Francois, M Van Den Abbeele, T Mosca-Boidron, A L Faivre, L Shimoda, Y Watanabe, K Bonneau, D Rastam, M Leboyer, M Scherer, S W Gillberg, C Delorme, R Cloëz-Tayarani, I Bourgeron, T Mol Psychiatry Original Article 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. Nature Publishing Group 2017-04 2016-05-10 /pmc/articles/PMC5378808/ /pubmed/27166760 http://dx.doi.org/10.1038/mp.2016.61 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Mercati, O Huguet, G Danckaert, A André-Leroux, G Maruani, A Bellinzoni, M Rolland, T Gouder, L Mathieu, A Buratti, J Amsellem, F Benabou, M Van-Gils, J Beggiato, A Konyukh, M Bourgeois, J-P Gazzellone, M J Yuen, R K C Walker, S Delépine, M Boland, A Régnault, B Francois, M Van Den Abbeele, T Mosca-Boidron, A L Faivre, L Shimoda, Y Watanabe, K Bonneau, D Rastam, M Leboyer, M Scherer, S W Gillberg, C Delorme, R Cloëz-Tayarani, I Bourgeron, T CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title | CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title_full | CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title_fullStr | CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title_full_unstemmed | CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title_short | CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
title_sort | cntn6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378808/ https://www.ncbi.nlm.nih.gov/pubmed/27166760 http://dx.doi.org/10.1038/mp.2016.61 |
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