ATXN1 intermediate-length polyglutamine expansions are associated with amyotrophic lateral sclerosis

NEUROBIOLOGY OF AGING

卷:64

Article

Lattante, Serena¹  Pomponi, Maria Grazia¹  Conte, Amelia²  Marangi, Giuseppe¹  Bisogni, Giulia²  Patanella, Agata Katia²  Meleo, Emiliana²  Lunetta, Christian³  Riva, Nilo⁴  Mosca, Lorena⁵  Carrera, Paola⁶  Bee, Marco⁷  Zollino, Marcella¹  Sabatelli, Mario² 

[1] Catholic Univ, Sch Med, Inst Genom Med, Rome, Italy

[2] Catholic Univ, Sch Med, Inst Neurol, Clin Ctr NEMO Roma,Dept Geriatr Neurosci & Orthop, Largo A Gemelli 8, I-00168 Rome, Italy

[3] Fdn Serena Onlus, NeuroMuscular Omnictr, Milan, Italy

[4] Ist Sci San Raffaele, Inst Expt Neurol INSPE, Dept Neurol, Div Neurosci, Milan, Italy

[5] ASST Grande Osped Metropolitano Niguarda, Dept Lab Med, Med Genet, Milan, Italy

[6] Ist Sci San Raffaele, Div Genet & Cell Biol, Unit Genom Human Dis Diag, Milan, Italy

[7] Univ Trento, Dept Econ & Management, Trento, Italy

关键词: Amyotrophic lateral sclerosis;    Spinocerebellar ataxia;    Frontotemporal dementia;    ATXN1;    C9orf72;   

DOI  :  10.1016/j.neurobiolaging.2017.11.011

来源: Elsevier

【 摘 要 】

To clarify the possible involvement of intermediate ATXN1 alleles as risk factors for amyotrophic lateral sclerosis (ALS), we tested ATXN1 in a cohort of 1146 Italian ALS patients, previously screened for variants in other ALS genes, and in 529 controls. We detected ATXN1 alleles with >= 33 polyglutamine repeats in 105 of 1146 patients (9.16%) and 29 of 529 controls (5.48%) (p = 0.003). The frequency of ATXN1 alleles with >= 33 polyglutamine repeats was particularly high in the group of ALS patients carrying the C9orf72 expansion (12/59, 20.3%). We confirmed this result in an independent cohort of C9orf72 Italian patients (10/80 cases, 12.5%), thus finding a cumulative frequency of ATXN1 expansion of 15.82% in C9orf72 carriers (p = 2.40E-05). Our results strongly support the hypothesis that ATXN1 could act as a disease risk gene in ALS, mostly in C9orf72 expansion carriers. Further studies are needed to confirm our results and to define the mechanism by which ATXN1 might contribute to neuronal degeneration leading to ALS. (C) 2017 Elsevier Inc. All rights reserved.

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