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DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease.

Imma CastaldoMariarosaria De RosaAntonella RomanoCandida ZuchegnaFerdinando SquitieriRosella MechelliSilvio PelusoCristiana BorrelliAngelo Del MondoElena SalvatoreLuigi Angelo VescoviSimone MiglioreGiuseppe De MicheleGiovanni RistoriGiovanni RistoriEnrico Vittorio AvvedimentoAntonio Porcellini
Published in: Annals of neurology (2019)
Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301.
Keyphrases
  • dna damage
  • peripheral blood
  • genome wide
  • induced apoptosis
  • copy number
  • oxidative stress
  • cell death
  • mass spectrometry
  • transcription factor
  • cell proliferation
  • high resolution
  • neural network