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Novel Autism Susceptibility Gene Identified

Gene Important to Melatonin Synthesis is Mutated in Some Individuals with Autism
March 05, 2008

A team of scientists at the Pasteur Institute, led by Cure Autism Now funded researcher Thomas Bourgeron, has published a study in Molecular Psychiatry which identifies a new autism susceptibility gene, known as ASMT, which is involved in the production of melatonin from serotonin. The researchers studied a region shared by the X and Y chromosomes called the pseudoautosomal region 1 (PAR1). Deletions of the PAR1 region had been previously reported in patients with autism spectrum disorders, but the causative gene(s) were not identified.

In collaboration with INSERM, Robert Debré Hospital, Albert Chenevier hospital, and the department of psychiatry of the University of Gothenburg (Sweden), the group led by Thomas Bourgeron studied one gene in PAR1, named ASMT. This gene encodes an enzyme involved in melatonin synthesis. Melatonin, produced mainly during the night by the pineal gland, plays a crucial role in the regulation of the circadian (night/day) rhythms, such as the sleep-wake cycles. Low melatonin levels have been previously reported in individuals with ASD by three independent groups, but the cause remained unknown. In this new study, researchers observed that more than half of the children with ASD had low blood melatonin levels (less than half of the control value) and this low concentration was correlated with a deficit of the ASMT enzyme activity. Consistent with these functional studies, mutations of the ASMT gene, contributing to low expression of the ASMT protein and/or low ASMT enzyme activity, were identified in several families.

The authors of the study insist that the presence of low melatonin levels in an individual does not necessarily lead to autism and cannot be considered as a diagnostic test for the condition. Indeed, several parents of children with autism also have low melatonin levels, although they do not have autism. Thus, the consequences of low melatonin levels on brain function and development remain to be specified. Although just the first report of mutations in this specific biochemical pathway, this somewhat unexpected finding has opened up another entirely new avenue of research into autism. The scientists hypothesize that low melatonin could have a direct role on the modulation of neuronal networks and thus could amplify the effect of other genetic risk factors in affected individuals. Melatonin could also affect circadian rhythms and sleep-wake cycles, making the children more vulnerable to other still unidentified susceptibility factors. Indeed, sleep problems are very frequent in individuals with autism and two recent studies have shown that the use of melatonin seems to improve sleep.

Click here for the abstract from Molecular Psychiatry.