TY - JOUR
T1 - DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease
AU - Castaldo, Imma
AU - De Rosa, Mariarosaria
AU - Romano, Antonella
AU - Zuchegna, Candida
AU - Squitieri, Ferdinando
AU - Mechelli, Rosella
AU - Peluso, Silvio
AU - Borrelli, Cristiana
AU - Del Mondo, Angelo
AU - Salvatore, Elena
AU - Vescovi, Luigi Angelo
AU - Migliore, Simone
AU - De Michele, Giuseppe
AU - Ristori, Giovanni
AU - Romano, Silvia
AU - Avvedimento, Enrico Vittorio
AU - Porcellini, Antonio
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.25393
DO - 10.1002/ana.25393
M3 - Article
AN - SCOPUS:85059952914
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
ER -