atxn2 and its neighbouring gene sh2b3 are associated with increased als risk in the turkish populationatxn2基因及其邻近sh2b3土耳其与als发病风险增加的人口.pdf

ATXN2 and Its Neighbouring Gene SH2B3 Are Associated with Increased ALS Risk in the Turkish Population 1. ¨ ¨ ¨ ¨ 1. ¨ ¨ 1 ˘ 1 ¨ ˘ 1 2 Suna Lahut , Ozgur Omur , Ozgun Uyan , Zeynep Sena Agım , Aslihan Ozoguz , Yes¸im Parman , 2 2 3 ¨ 4 5 1 Feza Deymeer , Piraye Oflazer , Filiz Koc¸ , Hilmi Ozc¸elik , Georg Auburger , A. Nazlı Bas¸ak * ˘ 1 Bogazic¸i University, Molecular Biology and Genetics Department, Neurodegeneration Research Laboratory, Istanbul, Turkey, 2 Istanbul University, Istanbul Medical School, Neurology Department, Istanbul, Turkey, 3 C¸ ukurova University, Medical School, Neurology Department, Adana, Turkey, 4 University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada, 5 Goethe University, Experimental Neurology, Frankfurt am Main, Germany Abstract Expansions of the polyglutamine (polyQ) domain ($34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1–4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In a