Abstract
BackgroundThere is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.MethodsWe analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.ResultsWe did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.ConclusionsOur results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.
Highlights
There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850)
All patients had an extensive evaluation by neurologists and clinical geneticists along with an intensive laboratory workup including standard karyotyping, fragile-X molecular testing and subtelomeric and targeted Multiplex LigationDependent Probe amplification (MLPA) assays, molecular karyotyping by microarray comparative genomic hybridization in 2/3 of cases, as well as metabolic and brain imaging studies in cases where clinically indicated
The present study aimed to provide more evidence to support the role of mitochondrial DNA (mtDNA) mutations or polymorphisms in ASD by screening one of the largest cohort of patients analysed to date
Summary
There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). The study by Oliveira et al [2] found that 7% of children in a population-based survey of school-age children with ASD met the criteria for mitochondrial respiratory chain disorders, and that they were clinically indistinguishable from other children with ASD This already recognized feature of ASD has lead several researchers to analyse mutations of the mtDNA as potential risk factors in ASD. Pons et al [11] explored the association of mtDNA mutations with autistic spectrum disorders, with special emphasis on mutation A3243G and mtDNA depletion These authors reported two ASD patients bearing the 3243A > G mutation located in the mtDNA tRNALeu(UUR) gene. According to Pons et al [11], ASD with or without additional neurological features can be an early presentation of the A3243G mutation and can be a prominent clinical manifestation of mtDNA depletion
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