RESUMEN
BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder. METHODS: We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease. RESULTS: A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9% of the cohort) and GRN (8.4%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups: type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1). CONCLUSION: These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation.
Asunto(s)
Demencia/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación , Proteínas tau/genética , Adenosina Trifosfatasas/genética , Anciano , Anciano de 80 o más Años , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Demencia/patología , Complejos de Clasificación Endosomal Requeridos para el Transporte , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Enfermedad de la Neurona Motora/genética , Proteínas del Tejido Nervioso/genética , Pruebas Neuropsicológicas , Progranulinas , Proteína FUS de Unión a ARN/genética , Encuestas y Cuestionarios , Proteína que Contiene ValosinaRESUMEN
The aim of this paper is to present an overview of the evolution of Infant Mortality in Montreal and in the whole Province of Quebec, from 1885 to 1971, and to highlight factors which may have determined the differential decline during this period. Based on civil registers, quality and fiability of the results are first discussed. Compiling statistics on infant mortality was of great importance in so far as it enabled hygienists to justify baby welfare clinics and county health units. In Montreal, cultural context showed a powerful influence on infant mortality: more French Canadian infants died in their first year than in British and the Jews. Between 1920 and 1930, infant mortality rates in the Canadian metropolitan area declined in rural areas of the Province. After this period, these rates have declined even more rapidly.