PT - JOURNAL ARTICLE AU - Millecamps, Stéphanie AU - Boillée, Séverine AU - Le Ber, Isabelle AU - Seilhean, Danielle AU - Teyssou, Elisa AU - Giraudeau, Marine AU - Moigneu, Carine AU - Vandenberghe, Nadia AU - Danel-Brunaud, Véronique AU - Corcia, Philippe AU - Pradat, Pierre-François AU - Le Forestier, Nadine AU - Lacomblez, Lucette AU - Bruneteau, Gaelle AU - Camu, William AU - Brice, Alexis AU - Cazeneuve, Cécile AU - LeGuern, Eric AU - Meininger, Vincent AU - Salachas, François TI - Phenotype difference between ALS patients with expanded repeats in <em>C9ORF72</em> and patients with mutations in other ALS-related genes AID - 10.1136/jmedgenet-2011-100699 DP - 2012 Apr 01 TA - Journal of Medical Genetics PG - 258--263 VI - 49 IP - 4 4099 - http://jmg.bmj.com/content/49/4/258.short 4100 - http://jmg.bmj.com/content/49/4/258.full SO - J Med Genet2012 Apr 01; 49 AB - Background Expanded GGGGCC hexanucleotide repeats in the promoter of the C9ORF72 gene have recently been identified in frontotemporal dementia (FTD), Amyotrophic Lateral Sclerosis (ALS) and ALS-FTD and appear as the most common genetic cause of familial (FALS) and sporadic (SALS) forms of ALS.Methods We searched for the C9ORF72 repeat expansion in 950 French ALS patients (225 FALS and 725 SALS) and 580 control subjects and performed genotype-phenotype correlations.Results The repeat expansion was present in 46% of FALS, 8% of SALS and 0% of controls. Phenotype comparisons were made between FALS patients with expanded C9ORF72 repeats and patients carrying another ALS-related gene (SOD1, TARDBP, FUS) or a yet unidentified genetic defect. SALS patients with and without C9ORF72 repeat expansions were also compared. The C9ORF72 group presented more frequent bulbar onset both in FALS (p&lt;0.0001 vs SOD1, p=0.002 vs TARDBP, p=0.011 vs FUS, p=0.0153 vs other FALS) and SALS (p=0.047). FALS patients with C9ORF72 expansions had more frequent association with FTD than the other FALS patients (p&lt;0.0001 vs SOD1, p=0.04 vs TARDBP, p=0.004 vs FUS, p=0.03 vs other FALS). C9ORF72-linked FALS patients presented an older age of onset than SOD1 (p=0.0139) or FUS mutation (p&lt;0.0001) carriers. Disease duration was shorter for C9ORF72 expansion carriers than for SOD1 (p&lt;0.0001) and TARDBP (p=0.0242) carriers, other FALS (p&lt;0.0001) and C9ORF72-negative SALS (p=0.0006).Conclusions Our results confirm the major role of expanded repeats in C9ORF72 as causative for ALS and provide evidence for specific phenotypic aspects compared to patients with other ALS-related genes.