ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

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• 作者：Giuseppe Borghero^a ; ¹ ; Maura Pugliatti^b ; ¹ ; Francesco Marrosu^a ; Maria Giovanna Marrosu^c ; Maria Rita Murru^c ; Gianluca Floris^a ; Antonino Cannas^a ; Leslie D. Parish^b ; Tea B. Cau^d ; Daniela Loi^d ; Anna Ticca^e ; Sebastiano Traccis^f ; Umberto Manera^g ; Antonio Canosa^g ; ^h ; Cristina Moglia^g ; Andrea Calvo^g ; ⁱ ; Marco Barberis^g ; ^j ; Maura Brunetti^g ; ^j ; Alan E. Renton^k ; Mike A. Nalls^l ; Bryan J. Traynor^j ; ^m ; Gabriella Restagno^j ; Adriano Chiò ; ^g ; ⁱ ; ⁿ ; ^{achio@usa.net" class="auth_mail" title="E-mail the corresponding author} ; for the ITALSGEN ; SARDINALS consortia²
• 关键词：Amyotrophic lateral sclerosis ; Ataxin 2 gene ; Genetic modifier
• 刊名：Neurobiology of Aging
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：36
• 期：10
• 页码：2906.e1-2906.e5
• 全文大小：438 K

文摘

Intermediate-length CAG expansions (encoding 27–33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival.