Extensive genetics of ALS A population-based study in Italy

被引：133

作者：

Chio, Adriano ^{[1
]}

Calvo, Andrea ^{[1
]}

Mazzini, Letizia ^{[2
]}

Cantello, Roberto ^{[2
]}

Mora, Gabriele ^{[4
]}

Moglia, Cristina ^{[1
]}

Corrado, Lucia ^{[3
]}

D'Alfonso, Sandra ^{[3
]}

Majounie, Elisa ^{[5
]}

Renton, Alan ^{[5
]}

Pisano, Fabrizio ^{[6
,7
,8
]}

Ossola, Irene ^{[9
]}

Brunetti, Maura

Traynor, Bryan J. ^{[5
]}

Restagno, Gabriella ^{[9
]}

机构：

[1] Univ Turin, Dept Neurosci, ALS Ctr, Turin, Italy

[2] Amedeo Avogadro Univ, Dept Neurol, ALS Ctr, Novara, Italy

[3] A Avogadro Univ, IRCAD, Dept Med Sci, Novara, Italy

[4] Sci Inst Milano, Milan, Italy

[5] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[6] IRCCS, Salvatore Maugeri Fdn, Dept Neurol, Pavia, Italy

[7] IRCCS, Salvatore Maugeri Fdn, Dept Neurorehab, Pavia, Italy

[8] Sci Inst Veruno, Veruno, Italy

[9] AO OIRM St Anna, Mol Genet Lab, Turin, Italy

来源：

NEUROLOGY | 2012年 / 79卷 / 19期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; CLINICAL CHARACTERISTICS; SOD1; MUTATIONS; FUS MUTATIONS; ANG GENE; C9ORF72; TARDBP; EPIDEMIOLOGY; DIAGNOSIS;

D O I：

10.1212/WNL.0b013e3182735d36

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset <= 54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that similar to 11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease. Neurology (R) 2012;79:1983-1989

引用

页码：1983 / 1989

页数：7

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