title: The modulation of Amyotrophic Lateral Sclerosis risk by ataxin-2 intermediate polyglutamine expansions is a specific effect.
abstract: Full expansions of the polyglutamine domain (polyQ≥34) within the polysome-associated protein ataxin-2 (ATXN2) are the cause of a multi-system neurodegenerative disorder, which usually presents as a Spino-Cerebellar Ataxia and is therefore known as SCA2, but may rarely manifest as Levodopa-responsive Parkinson syndrome or as motor neuron disease. Intermediate expansions (27≤polyQ≤33) were reported to modify the risk of Amyotrophic Lateral Sclerosis (ALS). We have now tested the reproducibility and the specificity of this observation. In 559 independent ALS patients from Central Europe, the association of ATXN2 expansions (30≤polyQ≤35) with ALS was highly significant. The study of 1490 patients with Parkinson's disease (PD) showed an enrichment of ATXN2 alleles 27/28 in a subgroup with familial cases, but the overall risk of sporadic PD was unchanged. No association was found between polyQ expansions in Ataxin-3 (ATXN3) and ALS risk. These data indicate a specific interaction between ATXN2 expansions and the causes of ALS, possibly through altered RNA-processing as a common pathogenic factor.
authors: Experimental Neurology, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Suzana
authors: S
authors: Gispert
authors: Alexander
authors: A
authors: Kurz
authors: Stefan
authors: S
authors: Waibel
authors: Peter
authors: P
authors: Bauer
authors: Inga
authors: I
authors: Liepelt
authors: Christof
authors: C
authors: Geisen
authors: Aaron D
authors: AD
authors: Gitler
authors: Tim
authors: T
authors: Becker
authors: Markus
authors: M
authors: Weber
authors: Daniela
authors: D
authors: Berg
authors: Peter M
authors: PM
authors: Andersen
authors: Rejko
authors: R
authors: Krüger
authors: Olaf
authors: O
authors: Riess
authors: Albert C
authors: AC
authors: Ludolph
authors: Georg
authors: G
authors: Auburger
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000067528:Ataxins; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D015203:Reproducibility of Results; D019680:Trinucleotide Repeat Expansion
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine