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De Novo Mutations in Ataxin-2 Gene and ALS Risk

2013; Public Library of Science; Volume: 8; Issue: 8 Linguagem: Inglês

10.1371/journal.pone.0070560

1932-6203

José Miguel Laffita‐Mesa, Jorge Michel Rodríguez Pupo, Raciel Moreno Sera, Yaimeé Vázquez Mojena, Vivian Kourí, Leonides Laguna-Salvia, Michael Martínez-Godales, José A. Valdevila Figueira, Peter Bauer, Roberto Rodríguez‐Labrada, Yanetza González Zaldívar, Martin Paucar, Per Svenningsson, Luis Velázquez‐Pérez,

Mitochondrial Function and Pathology

Pathogenic CAG repeat expansion in the ataxin-2 gene (ATXN2) is the genetic cause of spinocerebellar ataxia type 2 (SCA2). Recently, it has been associated with Parkinsonism and increased genetic risk for amyotrophic lateral sclerosis (ALS). Here we report the association of de novo mutations in ATXN2 with autosomal dominant ALS. These findings support our previous conjectures based on population studies on the role of large normal ATXN2 alleles as the source for new mutations being involved in neurodegenerative pathologies associated with CAG expansions. The de novo mutations expanded from ALS/SCA2 non-risk alleles as proven by meta-analysis method. The ALS risk was associated with SCA2 alleles as well as with intermediate CAG lengths in the ATXN2. Higher risk for ALS was associated with pathogenic CAG repeat as revealed by meta-analysis.