Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder

Autor: Evdokia Anagnostou, Alvin Loh, Andreas Schulze, Stephen W. Scherer, Wendy Roberts, Valeriy Levandovskiy, Jessie M. Cameron
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Amidinotransferases
Plasma Membrane Neurotransmitter Transport Proteins
lcsh:Chemistry
0302 clinical medicine
genetic variability
creatine deficiency syndrome
Prospective Studies
Child
Exome
lcsh:QH301-705.5
Spectroscopy
Exome sequencing
Genetics
education.field_of_study
General Medicine
Computer Science Applications
Guanidinoacetate N-methyltransferase
Autism spectrum disorder
Child
Preschool
Creatinine
Female
solute carrier family 6 member 8
autism spectrum disorder
glycine amidinotransferase
guanidinoacetate methyltransferase
Population
Nerve Tissue Proteins
Biology
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
medicine
Humans
Physical and Theoretical Chemistry
1000 Genomes Project
education
Molecular Biology
Organic Chemistry
Genetic Variation
medicine.disease
Minor allele frequency
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Autism
Guanidinoacetate N-Methyltransferase
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 18, Iss 8, p 1665 (2017)
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 18; Issue 8; Pages: 1665
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: