HTT gene intermediate alleles in neurodegeneration: evidence for association with Alzheimer's disease
Por:
Menendez-Gonzalez, M, Clarimon, J, Rosas-Allende, I, Blazquez, M, San Martin ES, Garcia-Fernandez, C, Lleo, A, Dols-Icardo, O, Illan-Gala, I, Moris, G, Ribacoba, R, Alvarez, V, Martinez, C
Publicada:
1 abr 2019
Resumen:
Huntington's disease (HD) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. Intermediate alleles (IAs) are in the range of 27-35 repeats and have been associated to a normal phenotype. The aim of this work was to analyze the association between intermediate huntingtin CAG-repeat alleles (IAs) and neurodegenerative diseases, other than HD. We screened the HTT CAG repeats in patients with Alzheimer's disease (AD) (n = 1126), Parkinson's disease (PD) (n = 610), and frontotemporal lobar degeneration (FTLD) (n = 225). We also studied 509 healthy controls (HCs). The relative frequency of IAs for each group was 6.03% in AD, 5.3% in FTLD, 3.5% in PD, and 2.9% in HCs. The frequency of IA was significantly higher among patients with AD when compared to HCs (p = 0.011, OR = 2.11, 95% CI = 1.19-3.74); no significant difference was observed in FTLD (p = 0.17; OR = 1.88, 95% CI = 0.85-4.03) and PD (p = 0.69; OR = 1.21; 95% CI (0.61-2.37) versus HCs. No atypical symptoms or clinical features distinctive of HD were found among carriers of IAs. We found 3 cases with CAG expansions within the pathological range, one diagnosed with AD, one with PD, and one with FTD. Results suggest that IAs might have a role in the pathogenesis of AD. In addition, HD patients might be misdiagnosed with other neurodegenerative diseases, particularly when CAG repeats are in the lower pathological range. (C) 2018 Elsevier Inc. All rights reserved.
Filiaciones:
Menendez-Gonzalez, M:
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
Clarimon, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau, Dept Neurol, Barcelona, Spain
Rosas-Allende, I:
Hosp Univ Cent Asturias, Lab Genet, Oviedo, Spain
Blazquez, M:
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
San Martin ES:
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Garcia-Fernandez, C:
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau, Dept Neurol, Barcelona, Spain
Dols-Icardo, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau, Dept Neurol, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Illan-Gala, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau, Dept Neurol, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Moris, G:
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Ribacoba, R:
Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain
Alvarez, V:
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Hosp Univ Cent Asturias, Lab Genet, Oviedo, Spain
Martinez, C:
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
Hosp Univ Cabuenes, Dept Neurol, Gijon, Spain
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