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Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations

Molecular Psychiatry volume 12, pages 977–979 (2007)Cite this article

Several studies have indicated that melatonin, a pineal gland hormone synthesized from serotonin, may play a role in autism spectrum disorders (ASDs). Children with autism have been observed to show pineal hypofunction, with low melatonin production and co-occurrence of sleep disturbances and altered circadian rhythms.1 Acetylserotonin O-methyltransferase (ASMT) is the enzyme involved in the last step of melatonin synthesis,2 and is encoded by the ASMT gene in the PAR1 region of the sex chromosomes. Recently, Melke et al.3 performed mutation screening of the ASMT gene in 250 individuals with ASDs and identified several rare variants with a likely functional role; these included a splice site mutation (IVS5+2T>C) present in two ASD families but not in 426 controls, which was associated with low ASMT activity and melatonin concentration. Moreover, significant association was reported for two single nucleotide polymorphisms (SNPs) located in one of the two alternative promoters of the gene (rs4446909 and rs5989681). For both SNPs, the major allele was more frequent in ASD cases compared to controls, and was associated with low ASMT transcript levels in lymphoblastoid cell lines. Taken together, these data suggested that ASMT gene variants might be involved in susceptibility to ASDs.

To investigate further these findings, we screened the ASMT gene in three independent collections of ASD families and controls: a Finnish population of 83 singleton and 44 multiplex families (127 affected individuals) and 100 Finnish controls; 69 individuals with ASD from Italian singleton families and 200 Italian controls; 194 unrelated individuals with ASD selected from multiplex families of the International Molecular Genetic Study of Autism Consortium (IMGSAC) collection, and 190 controls from the European Collection of Cell Cultures, both populations being mainly of UK ancestry.

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References

  1. Kulman G, Lissoni P, Rovelli F, Roselli MG, Brivio F, Sequeri P . Neuro Endocrinol Lett 2000; 20: 31–34.

    Google Scholar 

  2. Yi H, Dsonohue S, Klein D, McBride OW . Hum Mol Genet 1992; 2: 127–131.

    Article  Google Scholar 

  3. Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsater H et al. Mol Psychiatry 2007 (E-pub ahead of print, 15 May 2007; doi:10.1038/sj.mp.4002016).

    Article  Google Scholar 

  4. Auranen M, Vanhala R, Varilo T, Ayers K, Kempas E, Ylisaukko-oja T et al. Am J Hum Genet 2002; 71: 777–790.

    Article  Google Scholar 

  5. Ylisaukko-oja T, Nieminen-von Wendt T, Kempas E, Sarenius S, Varilo T, von Wendt L et al. Mol Psychiatry 2004; 9: 161–168.

    Article  CAS  Google Scholar 

  6. Bonora E, Lamb JA, Barnby G, Sykes N, Moberly T, Beyer KS et al. Eur J Hum Genet 2005; 13: 198–207.

    Article  CAS  Google Scholar 

  7. Barrett JC, Fry B, Maller J, Daly MJ . Bioinformatics 2005; 21: 263–265.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biology, University of Bologna, Bologna, Italy

    C Toma, F Blasi, E Bacchelli & E Maestrini

  2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland

    M Rossi, R Alen, R Vanhala & I Järvelä

  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    I Sousa & A P Monaco

Authors
  1. C Toma
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  2. M Rossi
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  3. I Sousa
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  6. R Alen
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  7. R Vanhala
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  8. A P Monaco
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  9. I Järvelä
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  10. E Maestrini
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International Molecular Genetic Study of Autism Consortium (IMGSAC)

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Correspondence to E Maestrini.

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Toma, C., Rossi, M., Sousa, I. et al. Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations. Mol Psychiatry 12, 977–979 (2007). https://doi.org/10.1038/sj.mp.4002069

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