Jauffrion) for technical assistance We thank C. Bouchier and S. Duthoy for the use of sequencing facilities at the Génopole Pasteur, B. Costes and N. Martin at the Genomic platform of the IMRB (M. Gossens) We thank E. Abadie, J. Deshommes and K. Le Dudal for their assistance. This work was supported by the Pasteur Institute, Agence Nationale pour la Recherche (ANR NEURO2006 -Project Manage_BPAD), EU grant QLG3-CT- 2002-01810 (EURO-MRX), and the RTRS Santé Mentale (Foundation FondaMental) ,
Creteil, F-94000, France. 6 Foundation Fondamental 7 Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre The Netherlands. 8 Center for Human Genetics, 3000 Leuven, Belgium. 9 Service de Biochimie, INSERM U942 10 Max Planck Institute for Molecular Genetics, Department Ropers CNRS, IEM, équipe « génétique expérimentale et moléculaire », université d'Orléans, pp.12-6218 ,
Imaging and Brain ,
18 University Paris- East, Faculty of Medicine, p.20 ,
Genetics and pathophysiology of mental retardation, European Journal of Human Genetics, vol.13, issue.6, pp.701-713, 2006. ,
DOI : 10.1016/j.neuron.2005.01.038
A review of the nature and treatment of sleep disorders in individuals with developmental disabilities???, Research in Developmental Disabilities, vol.22, issue.4, pp.255-272, 2001. ,
DOI : 10.1016/S0891-4222(01)00071-3
Sleep problems in children with mental handicap, Journal of Intellectual Disability Research, vol.10, issue.4, pp.269-290, 1991. ,
DOI : 10.1111/j.1365-2788.1991.tb00402.x
Stress, behaviour, and sleep problems in children with an intellectual disability, J Int Dev Dis, vol.25, pp.147-161, 2000. ,
Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis, Developmental Medicine & Child Neurology, vol.31, issue.5, pp.340-349, 2009. ,
DOI : 10.1111/j.1469-8749.2008.03244.x
Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters, Pharmacological Reviews, vol.55, issue.2, pp.325-395, 2003. ,
DOI : 10.1124/pr.55.2.2
Melatonin Suppresses Nighttime Memory Formation in Zebrafish, Science, vol.318, issue.5853, pp.1144-1146, 2007. ,
DOI : 10.1126/science.1148564
The basic physiology and pathophysiology of melatonin, Sleep Medicine Reviews, vol.9, issue.1, pp.11-24, 2005. ,
DOI : 10.1016/j.smrv.2004.08.001
Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion, Nature Genetics, vol.151, issue.1, pp.82-88, 2009. ,
DOI : 10.1086/521580
A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk, Nature Genetics, vol.49, issue.1, pp.89-94, 2009. ,
DOI : 10.1038/ng2088
Possible association between the androgen receptor gene and autism spectrum disorder, Psychoneuroendocrinology, vol.34, issue.5, pp.752-761, 2009. ,
DOI : 10.1016/j.psyneuen.2008.12.007
URL : https://hal.archives-ouvertes.fr/inserm-00390382
Importance and Relevance of Melatonin to Human Biological Rhythms, Journal of Neuroendocrinology, vol.265, issue.4, pp.427-431, 2003. ,
DOI : 10.1046/j.1365-2826.2003.00987.x
Melatonin in humans, N Engl J Med, vol.336, pp.186-195, 1997. ,
When Clocks Go Bad: Neurobehavioural Consequences of Disrupted Circadian Timing, PLoS Genetics, vol.17, issue.5, p.1000040, 2008. ,
DOI : 10.1371/journal.pgen.1000040.t001
Brief report: Circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism, Journal of Autism and Developmental Disorders, vol.272, issue.Suppl., pp.641-654, 1995. ,
DOI : 10.1007/BF02178193
Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder, Biological Psychiatry, vol.57, issue.2, pp.134-138, 2005. ,
DOI : 10.1016/j.biopsych.2004.11.003
Abnormal melatonin synthesis in autism spectrum disorders, Molecular Psychiatry, vol.280, issue.1, pp.90-98, 2008. ,
DOI : 10.1002/mrdd.20023
URL : https://hal.archives-ouvertes.fr/inserm-00166901
Evidence of pineal endocrine hypofunction in autistic children, Neuroendocrinol Lett, vol.21, pp.31-34, 2000. ,
The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders, Cold Spring Harbor Symposia on Quantitative Biology, vol.260, issue.1, pp.645-654, 2007. ,
DOI : 10.1038/sj.mp.4001629
Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations, Molecular Psychiatry, vol.21, issue.11, pp.977-979, 2007. ,
DOI : 10.1038/sj.mp.4002069
Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder, Journal of Pineal Research, vol.61, issue.4, pp.311-317, 2010. ,
DOI : 10.1111/j.1600-079X.2010.00754.x
Mutation screening of melatonin-related genes in patients with autism spectrum disorders, BMC Medical Genomics, vol.46, issue.1, p.10, 2010. ,
DOI : 10.1111/j.1600-079X.2008.00659.x
Identification of Pathway-Biased and Deleterious Melatonin Receptor Mutants in Autism Spectrum Disorders and in the General Population, PLoS ONE, vol.58, issue.7, p.11495, 2010. ,
DOI : 10.1371/journal.pone.0011495.s003
Melatonin regulates neuronal plasticity in the hippocampus, Journal of Neuroscience Research, vol.12, issue.4, pp.454-460, 2003. ,
DOI : 10.1002/jnr.10605
Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors, Nat Neurosci, vol.2, pp.401-403, 1999. ,
Individual Differences in the Amount and Timing of Salivary Melatonin Secretion, PLoS ONE, vol.28, issue.3, p.3055, 2008. ,
DOI : 10.1371/journal.pone.0003055.t003