<i>De Novo</i> Mutations in Ataxin-2 Gene and ALS Risk

<div><p>Pathogenic CAG repeat expansion in the ataxin-2 gene (<i>ATXN2</i>) 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 <i>de novo</i> mutations in <i>ATXN2</i> with autosomal dominant ALS. These findings support our previous conjectures based on population studies on the role of large normal <i>ATXN2</i> alleles as the source for new mutations being involved in neurodegenerative pathologies associated with CAG expansions. The <i>de novo</i> 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 <i>ATXN2</i>. Higher risk for ALS was associated with pathogenic CAG repeat as revealed by meta-analysis.</p>