Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients

被引：114

作者：

Lee, Teresa ^{[1
]}

Li, Yun R. ^{[1
]}

Ingre, Caroline ^{[2
]}

Weber, Markus ^{[4
,5
]}

Grehl, Torsten ^{[6
]}

Gredal, Ole ^{[7
]}

de Carvalho, Mamede ^{[8
]}

Meyer, Thomas ^{[9
]}

Tysnes, Ole-Bjorn ^{[10
]}

Auburger, Georg ^{[11
]}

Gispert, Suzana ^{[11
]}

Bonini, Nancy M. ^{[12
]}

Andersen, Peter M. ^{[2
,3
]}

Gitler, Aaron D. ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA

[2] Umea Univ, Dept Neurol, S-90187 Umea, Sweden

[3] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany

[4] Kantonspital St Gallen, Neuromuscular Dis Unit, St Gallen, Switzerland

[5] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland

[6] Ruhr Univ Bochum, Univ Hosp Bergmannsheil, Dept Neurol, Bochum, Germany

[7] Rehabil Ctr Neuromuscular Dis, Copenhagen, Denmark

[8] Fac Med, Inst Mol Med, Neuromuscular Unit, Lisbon, Portugal

[9] Charite, Dept Neurol, Berlin, Germany

[10] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway

[11] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany

[12] Univ Penn, Howard Hughes Med Inst, Dept Biol, Philadelphia, PA 19104 USA

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 09期

基金：

美国国家卫生研究院;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; SPINOCEREBELLAR ATAXIA; TRINUCLEOTIDE REPEAT; MUTATIONS; PROTEIN; GENE; TYPE-2; DEGENERATION; MANAGEMENT;

D O I：

10.1093/hmg/ddr045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease primarily affecting motor neurons. We recently identified intermediate-length polyglutamine (polyQ) expansions (27-33 Qs) in ataxin 2 as a genetic risk factor for sporadic ALS in North American ALS patients. To extend these findings, we assessed the ataxin 2 polyQ repeat length in 1294 European ALS patients and 679 matched healthy controls. We observed a significant association between polyQ expansions and ALS (> 30 Qs; P = 6.2 x 10(-3)). Thus, intermediate-length ataxin 2 polyQ repeat expansions are associated with increased risk for ALS also in the European cohort. The specific polyQ length cutoff, however, appears to vary between different populations, with longer repeat lengths showing a clear association. Our findings support the hypothesis that ataxin 2 plays an important role in predisposing to ALS and that polyQ expansions in ataxin 2 are a significant risk factor for the disease.

引用

页码：1697 / 1700

页数：4

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