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DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease
Author(s) -
Castaldo Imma,
De Rosa Mariarosaria,
Romano Antonella,
Zuchegna Candida,
Squitieri Ferdinando,
Mechelli Rosella,
Peluso Silvio,
Borrelli Cristiana,
Del Mondo Angelo,
Salvatore Elena,
Vescovi Luigi Angelo,
Migliore Simone,
De Michele Giuseppe,
Ristori Giovanni,
Romano Silvia,
Avvedimento Enrico Vittorio,
Porcellini Antonio
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25393
Subject(s) - peripheral blood , disease , peripheral , huntington's disease , medicine , pathology , biology , immunology
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.