Screening of the intronic expansion in the C9 orf72 gene and the ATXN2 mutation in Argentine patients diagnosed with Amyotrophic Lateral Sclerosis (P2.056)

OBJECTIVE: To estimate the frequency of the expansion of the C9orf72 gene and the ATXN2 mutation in a cohort of 77 consecutive ALS patients from Argentina. BACKGROUND: The intronic expansion in the C9orf72 gene has been identified as a major cause of ALS, presenting a frequency of 5-7[percnt] in sporadic ALS and of 30-40[percnt] in familial forms in European populations. ATXN2 mutation has recently been associated with increased risk of developing the illness. These mutations had never been explored in our country. DESIGN/METHODS: We evaluated 77 Argentine patients with ALS, fulfilling El Escorial criteria. Forty one were men. Mean age was 57,2 years. Six patients had familial ALS and one showed association with frontotemporal dementia. DNA from peripheral blood was extracted according to standard methods. The genetic study was performed by repeat-primed PCR and fragment analysis. RESULTS: More than 30 repeats expansions in C4G2 C9orf72 gene were found only in 3 sporadic patients (2.1[percnt]). An heterozygous expansion of ATXN 2 of 22-27 repetitions was identified in 3 patients; all of whom presented a familial form of the disease. CONCLUSIONS: We report the first 3 cases of ALS carriers of C9orf72 repeat expansion in Argentina and 3 intermediate expansions in the ATXN2 gene which confer an increased risk of developing ALS. Disclosure: Dr. Tillard has nothing to disclose. Dr. Cisneros has nothing to disclose. Dr. Marchesoni has nothing to disclose. Dr. Pardal has nothing to disclose. Dr. Schottlaender has nothing to disclose. Dr. Houlden has nothing to disclose. Dr. M has nothing to disclose. Dr. Conti has nothing to disclose. Dr. Jose has nothing to disclose. Dr. Carnero has nothing to disclose. Dr. Perez Akly has nothing to disclose. Dr. Nogues has nothing to disclose. Dr. Uchitel has nothing to disclose. Dr. de Ambrosi has nothing to disclose. Dr. Lautre has nothing to disclose. Dr. Barroso has nothing to disclose. Dr. Dubrovsky has nothing to disclose. Dr. Pirra has nothing to disclose. Dr. Jauregui has nothing to disclose. Dr. Landriscina has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Goyeneche has nothing to disclose. Dr. Mazia has nothing to disclose. Dr. Salutto has nothing to disclose. Dr. Nofal has nothing to disclose. Dr. Salazar has nothing to disclose. Dr. Brand has nothing to disclose. Dr. Surace has nothing to disclose. Dr. Reisin has received personal compensation for activities with Shire Pharmaceuticals Group as a consultant.