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B28 Combined replication malfunctions in huntington’s disease
  1. Zoltan Grosz1,
  2. Danuta Szirmai2,
  3. Viktória Reményi2,
  4. Renáta Bencsik2,
  5. Judit Mária Molnár2
  1. 1Institute of Genomic Medicine and Rare Diseases, Budapest, Hungary
  2. 2Semmelweis University, Budapest, Hungary

Abstract

Background Huntington’s disease (HD) is a monogenic disease caused by the CAG repeat expansion of the IT15 gene. The underlying molecular mechanism of the disease is related to the toxic huntingtin protein aggregates. Mitochondrial dysfunction was observed, as well. The involvement and role of mitochondrial repair mechanism in the disease pathogenesis is not widely studied. RAD51 is one of the genes playing a role in the mitochondrial DNA repair mechanism of cells.

Aims To use a genomic approach to better understand the mitochondrial dysfunction observed in HD. We examined the presence of mt DNA deletion and in positive cases RAD51 gene in genetically confirmed Huntington’s patients assuming that besides IT15 mutation other genetic factors might be responsible for disease manifestation.

Methods One hundred genetically confirmed HD patients were compared to two control groups that included 100 subjects each. One of the contol groups was patients included PMP22 deletion/duplication, while the other was made up from healty subjects. Mt DNA deletion was diagnosed with long PCR technic. RAD51 gene were analysed by direct Sanger sequencing.

Results Mt DNA deletion was found in 25 cases regarding Huntington’s disease patients and 12 cases in PMP22 copy number variants group, while among healthy controls there were only 6 cases.

The mt DNA deletion was not correlated with age in any of the cohorts. No mutation in RAD51gene was detected.

Conclusion Mutation of mt DNA is significantly higher in the HD group, but mutations in gene RAD51 responsible for mitochondrial repair were not detected. It would be worth to consider analysing other genes playing a role in the mitochondrial repair mechanism.

  • mitochondrial dysfunction
  • repair mechanism

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