De novo mutations in ataxin-2 gene and ALS risk.
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.
Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba. laffita@ataxia.hlg.sld.cu
José Miguel
JM
Laffita-Mesa
Jorge Michel
JM
Rodríguez Pupo
Raciel
R
Moreno Sera
Yaimee
Y
Vázquez Mojena
Vivian
V
Kourí
Leonides
L
Laguna-Salvia
Michael
M
Martínez-Godales
José A
JA
Valdevila Figueira
Peter O
PO
Bauer
Roberto
R
Rodríguez-Labrada
Yanetza
Y
González Zaldívar
Martin
M
Paucar
Per
P
Svenningsson
Luís
L
Velázquez Pérez
D000328:Adult; D000368:Aged; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000067528:Ataxins; D001483:Base Sequence; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010455:Peptides / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
D000067528:Ataxins; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine