C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population

NEUROBIOLOGY OF AGING

卷:33

Article

Sabatelli, Mario^2,3  Conforti, Francesca Luisa^4,5  Zollino, Marcella⁶  Mora, Gabriele⁷  Monsurro, Maria Rosaria⁸  Volanti, Paolo⁹  Marinou, Kalliopi⁷  Salvi, Fabrizio¹⁰  Corbo, Massimo¹¹  Giannini, Fabio¹²  Battistini, Stefania¹²  Penco, Silvana¹³  Lunetta, Christian¹¹  Quattrone, Aldo^4,5  Gambardella, Antonio^4,5  Logroscino, Giancarlo¹⁴  Simone, Isabella¹⁴  Bartolomei, Ilaria¹⁰  Pisano, Fabrizio¹⁵  Tedeschi, Gioacchino⁸  Conte, Amelia^2,3  Spataro, Rossella¹⁶  La Bella, Vincenzo¹⁶  Caponnetto, Claudia¹⁷  Mancardi, Gianluigi¹⁷  Mandich, Paola¹⁷  Sola, Patrizia^18,19  Mandrioli, Jessica^18,19  Renton, Alan E.²⁰  Majounie, Elisa²¹  Abramzon, Yevgeniya²⁰  Marrosu, Francesco^22,23  Marrosu, Maria Giovanna²⁴  Murru, Maria Rita²⁴  Sotgiu, Maria Alessandra²⁵  Pugliatti, Maura²⁶  Rodolico, Carmelo²⁷  Moglia, Cristina¹  Calvo, Andrea¹  Ossola, Irene²⁸  Brunetti, Maura²⁸  Traynor, Bryan J.²⁰  Borghero, Giuseppe^22,23  Restagno, Gabriella²⁸  Chio, Adriano¹ 

[1] Univ San Giovanni Battista Turin, Univ Turin, Azienda Osped, Dept Neurosci, Turin, Italy

[2] Catholic Univ, Neurol Inst, Rome, Italy

[3] ICOMM Assoc ALS Res, Rome, Italy

[4] CNR, Inst Neurol Sci, Cosenza, Italy

[5] Univ Magna Grecia, Catanzaro, Italy

[6] Univ Cattolica Sacro Cuore, Mol Genet Lab, Rome, Italy

[7] Sci Inst Milan, Salvatore Maugeri Fdn IRCSS, Milan, Italy

[8] Univ Naples 2, Dept Neurol Sci, Naples, Italy

[9] Sci Inst Mistretta, Salvatore Maugeri Fdn IRCSS, Mistretta, Italy

[10] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, Bologna, Italy

[11] Serena Fdn, Neuromuscular OnmiCtr, Milan, Italy

[12] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy

[13] Osped Niguarda Ca Granda, Dept Lab Med, Milan, Italy

[14] Univ Bari, Dept Neurosci, Bari, Italy

[15] Sci Inst Veruno, Salvatore Maugeri Fdn IRCSS, Veruno, Italy

[16] Univ Palermo, ALS Clin Res Ctr, Bio Ne C, Palermo, Italy

[17] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy

[18] St Agostino Estense Hosp, Dept Neurosci, Modena, Italy

[19] Univ Modena, I-41100 Modena, Italy

[20] NIA, Mol Genet Unit, Neurogenet Lab, Bethesda, MD 20892 USA

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

[22] Azienda Univ Osped Cagliari, Cagliari, Italy

[23] Univ Cagliari, Cagliari, Italy

[24] Univ Cagliari, Ctr Sclerosi Multipla, Osped Binaghi, Cagliari, Italy

[25] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy

[26] Univ Sassari, Dept Neurosci, I-07100 Sassari, Italy

[27] Univ Messina, Dept Neurosci Psychiat & Anaesthesiol Sci, Messina, Italy

[28] ASO OIRM St Anna, Dept Clin Pathol, Mol Genet Unit, Turin, Italy

关键词: Amyotrophic lateral sclerosis;    C9ORF72;    Frontotemporal dementia;    Survival;   

DOI  :  10.1016/j.neurobiolaging.2012.02.011

来源: Elsevier

【 摘 要 】

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally matched control samples (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the most common mutation in Italy and the second most common in Sardinia. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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