RESUMO
Human induced pluripotent stem cell (hiPSC) line INEUi001-A was reprogrammed from peripheral blood mononuclear cells (PBMC) using the lentiviral-hSTEMCCA-loxP vector. PBMCs were obtained from a 75- year-old female ALS/FTD disease patient carrying a heterozygous deletion within the C9ORF72 hexanucleotide repeat region resulting in a GGGGCCG sequence (â¼1.16 repeats). C9ORF72 genotype was maintained and stemness and pluripotency confirmed in INEUi001-A hiPSC line.
Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Células-Tronco Pluripotentes Induzidas , Feminino , Humanos , Idoso , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Demência Frontotemporal/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteína C9orf72/genética , Leucócitos Mononucleares/metabolismo , GenótipoRESUMO
Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overall expansion frequency of 18.2% (6 of 33 unrelated cases). Moreover, the C9orf72 expansion accounted for 37.5% of all familial FTD cases (6 of 16 families). The expansion frequency in sporadic ALS cases was 2% (1 of 47 unrelated patients), whereas we observed the expansion in 1 of 3 families with a positive history for ALS. Overall, the expansion frequency in our FTD group was similar to that reported for patients in Europe and North America, whereas the frequency in our sporadic ALS group was significantly lower. To our knowledge, this is the first report on the frequency of the C9orf72 expansion in a Latin American population.