Abstract | BACKGROUND: One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene. METHODS: RESULTS: Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A, and MTNR1B. CONCLUSIONS: Our report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.
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Authors | Lina Jonsson, Elin Ljunggren, Anna Bremer, Christin Pedersen, Mikael Landén, Kent Thuresson, Maibritt Giacobini, Jonas Melke |
Journal | BMC medical genomics
(BMC Med Genomics)
Vol. 3
Pg. 10
(Apr 08 2010)
ISSN: 1755-8794 [Electronic] England |
PMID | 20377855
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Melatonin
- Melatonin
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Topics |
- Amino Acid Sequence
- Child
- Child Development Disorders, Pervasive
(genetics, metabolism)
- Cohort Studies
- Conserved Sequence
- Female
- Genetic Testing
- Humans
- Male
- Melatonin
(metabolism)
- Molecular Sequence Data
- Mutation
- Receptors, Melatonin
(chemistry, genetics)
- Sequence Alignment
- Signal Transduction
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