Next Article in Journal
Tricetin Induces Apoptosis of Human Leukemic HL-60 Cells through a Reactive Oxygen Species-Mediated c-Jun N-Terminal Kinase Activation Pathway
Previous Article in Journal
Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays
Previous Article in Special Issue
Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(8), 1665; doi:10.3390/ijms18081665

Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder

1
Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, Toronto, ON M5G 0A4, Canada
2
Department of Paediatrics, University of Toronto, Toronto, ON M5S 1A1, Canada
3
Holland Bloorview Kids Rehabilitation Hospital, 150 Kigour Rd, Toronto, ON M4G 1R8, Canada
4
The Centre for Applied Genomics and Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
5
McLaughlin Centre and Department of Molecular Genetics, 686 Bay Street, 13th Floor, Peter Gilgan Center for Research and Learning, Toronto, ON M5G 0A4, Canada
6
Surrey Place Center, 2 Surrey Place, Toronto, ON M5S 2C2, Canada
7
Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
*
Author to whom correspondence should be addressed.
Received: 5 May 2017 / Revised: 19 July 2017 / Accepted: 25 July 2017 / Published: 31 July 2017
View Full-Text   |   Download PDF [2713 KB, uploaded 1 August 2017]   |  

Abstract

Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase (GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase (GAMT gene), and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher’s exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum disorder (ASD) in children. View Full-Text
Keywords: autism spectrum disorder; creatine deficiency syndrome; glycine amidinotransferase; guanidinoacetate methyltransferase; solute carrier family 6 member 8; genetic variability autism spectrum disorder; creatine deficiency syndrome; glycine amidinotransferase; guanidinoacetate methyltransferase; solute carrier family 6 member 8; genetic variability
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cameron, J.M.; Levandovskiy, V.; Roberts, W.; Anagnostou, E.; Scherer, S.; Loh, A.; Schulze, A. Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder. Int. J. Mol. Sci. 2017, 18, 1665.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top