RESUMEN
Induced pluripotent stem cell (iPSC) line were generated from erythroblasts of a Brazilian patient with familiar form of amyotrophic lateral sclerosis (ALS). NGS analysis demonstrated that patient carried a mutation in SOD1 gene, as well as a deletion in FUS gene. CytoTune™-iPS 2.0 Sendai Reprogramming Kit (containing the reprogramming factors OCT3/4, KLF4, SOX2 and cMYC) was used to generate the cell lines. The iPSCs express pluripotency markers, have normal karyotype and differentiated spontaneously in the three germ layers. The expression of Sendai virus was lost in all iPSC lines after 15 passages.
Asunto(s)
Células Madre Pluripotentes Inducidas/citología , Esclerosis Amiotrófica Lateral/metabolismo , Brasil , Línea Celular , Humanos , Cariotipo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/metabolismo , Mutación/genética , Proteínas de Transporte de Catión Orgánico/metabolismo , Factores de Transcripción SOXB1/metabolismo , Superóxido Dismutasa-1/genéticaRESUMEN
Induced pluripotent stem cell (iPSC) lines were generated from erythroblasts of two patients with amyotrophic lateral sclerosis (ALS) and two healthy individuals. One familial and one sporadic ALS patients were used, both with genetic alterations in VAPB gene. CytoTune™-iPS 2.0 Sendai Reprogramming Kit (containing the reprogramming factors OCT3/4, KLF4, SOX2 and cMYC) was used to generate the iPSC cell lines. The four iPSCs express pluripotency markers, have normal karyotype and differentiated spontaneously in the three germ layers. The expression of Sendai virus was lost in all iPSC lines after 15 passages.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Diferenciación Celular , Reprogramación Celular , Células Madre Pluripotentes Inducidas/patología , Leucocitos Mononucleares/patología , Mutación , Proteínas de Transporte Vesicular/genética , Adulto , Esclerosis Amiotrófica Lateral/patología , Células Cultivadas , Voluntarios Sanos , Heterocigoto , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Factor 4 Similar a Kruppel , Leucocitos Mononucleares/metabolismo , Masculino , FenotipoRESUMEN
OBJECTIVE: The clinical and epidemiological profile of sporadic amyotrophic lateral sclerosis (ALS), a chronic, degenerative, progressive motor neuron disease of unknown etiology, was described and evaluated in the city of Rio de Janeiro. METHOD: Patients with a diagnosis definite of ALS according to the revised criteria of the El Escorial World Federation of Neurology were included in this retrospective, descriptive study (n=227). Demographic data, clinical variables, mortality and survival of these patients were assessed. RESULTS: Of the 227 included cases, 143 (63%) were male and 84 (37%) were female, resulting in a male/female ratio of 1.7:1. Mean age at onset of the disease was 53.6 ± 12.1 years, overall median survival time was 49 months (95%CI: 42.4-55.5) and the majority of patients (71.4%) were white, black patients 15.9% and mulattos 12.8%. The most common forms of the disease were classic and bulbar ALS. CONCLUSION: Taking classic and bulbar ALS together, the disease was more common in white, male patients of 50 to 70 years of age. When analyzed separately, the bulbar form was more common in women and in older patients. Survival of patients with bulbar ALS was shorter compared to that of patients with classic ALS.