Abnormal melatonin synthesis in autism spectrum disorders
| Autor: | Christopher Gillberg, Henrik Anckarsäter, Richard Delorme, Thomas Bourgeron, X Drouot, J.M. Launay, I. C. Gillberg, H Goubran Botros, Maria Råstam, Jonas Melke, Gudrun Nygren, Nadia Chabane, M-C Mouren-Simeoni, Pauline Chaste, F Chevalier, Catalina Betancur, Marion Leboyer, Ola Ståhlberg, Fabien Fauchereau, Christelle M. Durand, Corinne Collet |
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| Přispěvatelé: | Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Child and Adolescent Psychiatry, University of Gothenburg (GU), Institute of Clinical Sciences, Lund University [Lund], Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EA3621, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Saint George's Hospital Medical School, Université Paris Diderot - Paris 7 (UPD7), This work was supported by the Pasteur Institute, INSERM, Assistance Publique-Hôpitaux de Paris, Fondation France Télécom, Cure Autism Now, Fondation de France, Fondation biomédicale de la Mairie de Paris, Fondation pour la Recherche Médicale, Fondation NRJ and the Swedish Medical Research Council., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Betancur, Catalina |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
melatonin [SDV.GEN] Life Sciences [q-bio]/Genetics Pineal gland Exon 0302 clinical medicine Reference Values Child Promoter Regions Genetic Genetics 0303 health sciences Middle Aged HIOMT Pedigree Psychiatry and Mental health medicine.anatomical_structure Female medicine.drug Acetylserotonin O-Methyltransferase Adult circadian rhythm medicine.medical_specialty Adolescent Matched-Pair Analysis autism Biology Article Melatonin 03 medical and health sciences Cellular and Molecular Neuroscience ASMT Internal medicine mental disorders medicine Humans Circadian rhythm Autistic Disorder Allele sleep Molecular Biology 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics Polymorphism Genetic medicine.disease Developmental disorder Endocrinology Acetylserotonin O-methyltransferase Case-Control Studies Autism 030217 neurology & neurosurgery |
| Zdroj: | Molecular Psychiatry Molecular Psychiatry, Nature Publishing Group, 2008, 13 (1), pp.90-8. ⟨10.1038/sj.mp.4002016⟩ Molecular Psychiatry, 2008, 13 (1), pp.90-8. ⟨10.1038/sj.mp.4002016⟩ |
| ISSN: | 1359-4184 1476-5578 |
| DOI: | 10.1038/sj.mp.4002016⟩ |
| Popis: | International audience; Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.Molecular Psychiatry (2008) 13, 90-98; doi:10.1038/sj.mp.4002016; published online 15 May 2007. |
| Databáze: | OpenAIRE |
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