OBJECTIVE: To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. DESIGN: Case-control study. SETTING: France and Quebec, Canada. PARTICIPANTS: A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. RESULTS: We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. CONCLUSIONS: Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.
OBJECTIVE: To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. DESIGN: Case-control study. SETTING: France and Quebec, Canada. PARTICIPANTS: A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. RESULTS: We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. CONCLUSIONS: Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.
Authors: Marka van Blitterswijk; Bianca Mullen; Michael G Heckman; Matthew C Baker; Mariely DeJesus-Hernandez; Patricia H Brown; Melissa E Murray; Ging-Yuek R Hsiung; Heather Stewart; Anna M Karydas; Elizabeth Finger; Andrew Kertesz; Eileen H Bigio; Sandra Weintraub; Marsel Mesulam; Kimmo J Hatanpaa; Charles L White; Manuela Neumann; Michael J Strong; Thomas G Beach; Zbigniew K Wszolek; Carol Lippa; Richard Caselli; Leonard Petrucelli; Keith A Josephs; Joseph E Parisi; David S Knopman; Ronald C Petersen; Ian R Mackenzie; William W Seeley; Lea T Grinberg; Bruce L Miller; Kevin B Boylan; Neill R Graff-Radford; Bradley F Boeve; Dennis W Dickson; Rosa Rademakers Journal: Neurobiol Aging Date: 2014-05-02 Impact factor: 4.673