Frecuencia de la expansión hexanucleotídica G4C2 en el gen C9ORF72 y características clínicas de pacientes que consultaron a centros de referencia en ELA: resultados preliminares.

GARGIULO MONACHELLI GM; CLAIRE LEBLOND; MARIELA BETTINI; PATRICK A DION; MARCELO RUGIERO; GONZALEZ DENISELLE M.C; MIGUEL PAGANO; GUY ROULEAU

Congreso; 67º Annual Meeting of the American Academy of Neurology.; 2015

FREQUENCY OF THE EXPANDED HEXANUCLEOTIDE G4C2 REPEAT IN THE C9ORF72 GENE AND CLINICAL FEATURES OF PATIENTS PRESENTING TO ALS REFERRAL CENTERS IN BUENOS AIRES, ARGENTINA: PRELIMINARY RESULTS.Gisella Gargiulo-Monachelli (1,7), Claire S. LeBlond (2), Mariela Bettini (3), Javier Vasquez-Varela (1), Maria Alejandra Figueredo (4), Andrea Lautre (5), Patrick A. Dion (2), Maria Laura Garau (1), Marcelo Kauffman (6), Marcelo Rugiero (3), Ma. Claudia Gonzalez Deniselle (7), Miguel A. Pagano (1), Guy A. Rouleau (2).1. Servicio de Neurologia, Hospital J.A. Fernandez. 2. Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Qc, Canada. 3. Seccion Enfermedades Neuromusculares, Hospital Italiano de Buenos Aires. 4. Consultorio de enfermedades de motoneurona, Hospital San Roque y Hospital Español de La Plata. 5. Seccion Enfermedades Neuromusculares, Fundacion Favaloro. 6. Consultorio y Laboratorio de Neurogenetica. Centro Universitario de Neurologia JM Ramos Mejia. 7. Instituto de Biologia y Medicina Experimental (IBYME), UBA-CONICET.Objective: Our objective was to estimate the frequency of the expansion in a population of ALS and FTD patients in Argentina. Background: An intronic hexanucleotide G4C2 repeat expansion in the C9ORF72 gene has been shown to be the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in both familial and sporadic cases. Design/Methods: We analyzed the C9ORF72 expansion in 59 individual patients (46 sporadic +13 familial) seen consecutively in two ALS referral centers: 51 ALS (43+8), 3 FTD (0+3), and 5 ALS+FTD (3+2). Individual familial cases (n=13) represented 11 families. We used the RPPCR method and defined ≥30 repetitions as pathological (C9+). We considered familial disease based on presence of ALS, FTD or ALS+FTD in a first or second degree relative. We interrogated the nationality of parents and grandparents of the index case. Results: The C9+ expansion was found only in familial cases. In 2% (n=1) of ALS, 33% (n=1) of FTD and 40% (n=2) of ALS+FTD. Therefore, the frequency of sporadic C9+ cases was 0% and of familial cases was 27% (2 ALS+FTD, 1 ALS son of 1 FTD, i.e. 3/11). The age of onset was 32 years in ALS, 60 in FTD, 60 and 72 in ALS+FTD. The gender was male in the case of the ALS patient and female in all cases involving dementia. In the 3 patients with ALS criteria, onset of symptoms was bulbar, and the only pure ALS case had a rapid progression dying 8 months after diagnosis. The family history of disease in C9+ cases was: ALS, FTD, ALS+FTD, psychiatric disease and sudden death. The ethnicity in C9+ families was largely European (Italian and Spanish). Conclusions: Preliminary results suggest that the C9ORF72 expansion represents a rare cause of sporadic ALS in Argentina. C9+ cases involved patients with a positive family history of disease. C9+ ALS was associated with a young onset and rapid progression, bulbar onset and the co-existence of FTD and psychiatric disease.