Role of mitochondrial DNA variants in the development of fragile X-associated tremor/ataxia syndrome

Maria Isabel Alvarez-Mora, Cristina Santos, Lidia Carreño-Gago, Irene Madrigal, Maria Isabel Tejada, Francisco Martinez, Silvia Izquierdo-Alvarez, Elena Garcia-Arumi, Montserrat Mila, Laia Rodriguez-Revenga*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers of FMR1 premutation. Several studies have shown that mitochondrial dysfunction may play a role in neurodegenerative disorders. In order to assess whether mitochondrial DNA variants are involved in the risk of developing FXTAS we evaluated the frequency of mitochondrial haplogroups in 132 unrelated Spanish FMR1 premutation carriers. In addition, the entire mitogenome of 26 FMR1 premutation carriers was sequenced using massively parallel sequencing technologies to analyze mitochondrial DNA variants. Statistical analyses reveal a significant difference in the frequency of T haplogroup. Data analysis of mitochondrial DNA sequences evidence an association between FXTAS and the burden of heteroplasmic variants as well as their distribution. Our results suggest that haplogroup T might be a potential protective factor for FXTAS and that FXTAS individuals accumulate higher rates of heteroplasmic variants in compromised regions of the mitochondrial genome. These results may explain, in part, the role of mitochondrial DNA in the development of FXTAS.

Original languageEnglish
Pages (from-to)157-162
Number of pages6
Publication statusPublished - May 2020


  • FMR1 premutation
  • Low-level heteroplasmic variants
  • Mitogenome
  • mtDNA haplogroups
  • Risk factors


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