C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population

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• 作者：Mario Sabatelli^a ; ¹ ; Francesca Luisa Conforti^b ; ¹ ; Marcella Zollino^c ; ¹ ; Gabriele Mora^d ; ¹ ; Maria Rosaria Monsurrò ; ^e ; Paolo Volanti^f ; Kalliopi Marinou^d ; Fabrizio Salvi^g ; Massimo Corbo^h ; Fabio Gianniniⁱ ; Stefania Battistiniⁱ ; Silvana Penco^j ; Christian Lunetta^h ; Aldo Quattrone^b ; Antonio Gambardella^b ; Giancarlo Logroscino^k ; Isabella Simone^k ; Ilaria Bartolomei^g ; Fabrizio Pisano^l ; Gioacchino Tedeschi^e ; Amelia Conte^a ; Rossella Spataro^m ; Vincenzo La Bella^m ; Claudia Caponnettoⁿ ; Gianluigi Mancardiⁿ ; Paola Mandichⁿ ; Patrizia Sola^o ; Jessica Mandrioli^o ; Alan E. Renton^p ; Elisa Majounie^q ; Yevgeniya Abramzon^p ; Francesco Marrosu^r ; Maria Giovanna Marrosu^s ; Maria Rita Murru^s ; Maria Alessandra Sotgiu^t ; Maura Pugliatti^u ; Carmelo Rodolico^v ; ITALSGEN Consortium² ; Cristina Moglia^w ; Andrea Calvo^w ; Irene Ossola^x ; Maura Brunetti^x ; Bryan J. Traynor^p ; ^l ; Giuseppe Borghero^r ; ¹ ; Gabriella Restagno^x ; ¹ ; Adriano Chiò ; ^w ; ¹ ; ^{achio@usa.net}
• 关键词：Amyotrophic lateral sclerosis ; C9ORF72 ; Frontotemporal dementia ; Survival
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：August, 2012
• 卷：33
• 期：8
• 页码：1848.e15-1848.e20
• 文件大小：614 K

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.