RT Journal Article
SR Electronic
T1 Phenotype difference between ALS patients with expanded repeats in <em>C9ORF72</em> and patients with mutations in other ALS-related genes
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 258
OP 263
DO 10.1136/jmedgenet-2011-100699
VO 49
IS 4
A1 Millecamps, Stéphanie
A1 Boillée, Séverine
A1 Le Ber, Isabelle
A1 Seilhean, Danielle
A1 Teyssou, Elisa
A1 Giraudeau, Marine
A1 Moigneu, Carine
A1 Vandenberghe, Nadia
A1 Danel-Brunaud, Véronique
A1 Corcia, Philippe
A1 Pradat, Pierre-François
A1 Le Forestier, Nadine
A1 Lacomblez, Lucette
A1 Bruneteau, Gaelle
A1 Camu, William
A1 Brice, Alexis
A1 Cazeneuve, Cécile
A1 LeGuern, Eric
A1 Meininger, Vincent
A1 Salachas, François
YR 2012
UL http://jmg.bmj.com/content/49/4/258.abstract
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.