Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population.

Autor: Borrego-Hernández D; ALS Research Laboratory Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Vázquez-Costa JF; Neuromuscular Unit, ERN-NMD Group, Department of Neurology, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.; Department of Medicine, University of Valencia, 46010 Valencia, Spain., Domínguez-Rubio R; Motoneuron Functional Unit, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain., Expósito-Blázquez L; ALS Research Laboratory Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Aller E; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.; Genetics Department, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain., Padró-Miquel A; Genetics Laboratory (LCTMS), Bellvitge University Hospital-IDIBELL, 08908 L'Hospitalet de Llobregat, Spain., García-Casanova P; Neuromuscular Unit, ERN-NMD Group, Department of Neurology, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain., Colomina MJ; Anesthesia Service Unit, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain., Martín-Arriscado C; Clinical Research Unit, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Osta R; Laboratório de Genética e Biotecnologia (LAGENBIO), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Aragon Institute for Health Research (IIS Aragon), Zaragoza University, 50013 Zaragoza, Spain., Cordero-Vázquez P; ALS Research Laboratory Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Esteban-Pérez J; ALS Research Laboratory Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Povedano-Panadés M; Motoneuron Functional Unit, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain., García-Redondo A; ALS Research Laboratory Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2024 Feb 02; Vol. 12 (2). Date of Electronic Publication: 2024 Feb 02.
DOI: 10.3390/biomedicines12020356
Abstrakt: Intermediate CAG expansions in the gene ataxin-2 ( ATXN2 ) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.
Databáze: MEDLINE
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