Screening for mutations in GRN and MAPT and measurement of plasma progranulin in a Brazilian cohort of patients with frontotemporal lobar degeneration

• Grant number: 13/01758-4
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2013
• End date: June 30, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ricardo Nitrini
• Grantee: Ricardo Nitrini
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Jessica Ruivo Maximino ; LEONEL TADAO TAKADA ; Valéria Santoro Bahia

Abstract

The frontotemporal lobar degeneration (FTLD) clinical spectrum of disorders - behavioral variant of frontotemporal dementia, progressive non-fluent aphasia and semantic dementia - are the second most frequent cause of dementia in individuals aged 65 years or younger and around10% of patients have an autosomal dominant pattern of family history. The main genes associated with FTLDs are the progranulin gene (GRN), the tau protein gene (MAPT) and C9orf72. GRN mutations cause neurodegeneration by haploinsufficiency (with reductions in the plasma levels of the protein) and because of that, GRN mutations have been considered a plausible model for drug treatment, by using medications that increase progranulin levels. There have not been so far genetic studies in a Brazilian cohort of FTLD, and with the possibility of specific treatment options in the near future, the molecular diagnosis of these disorders is imperative. In this project, we propose screening for GRN and MAPT mutations and measurement of progranulin plasma levels in a Brazilian cohort of patients diagnosed with FTLD by physicians of the Cognitive and Behavioral Neurology Unit - Hospital das Clínicas - University of Sao Paulo Medical School. Our center is qualified to include patients with less frequent conditions such as the FTLDs. Our objective is to include 80 patients and 80 normal controls, and do clinical-genetic correlations in patients who are found to carry mutations. The genetic study of FTLDs will also allow us to collaborate in the future with other research institutions, allowing us to expand our DNA bank of patients with FTLDs. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAKADA, LEONEL T.; BAHIA, VALERIA S.; GUIMARAES, HENRIQUE C.; COSTA, THAIS V. M. M.; VALE, THIAGO C.; RODRIGUEZ, ROBERTA D.; PORTO, FABIO H. G.; MACHADO, JOAO C. B.; BEATO, ROGERIO G.; CESAR, KAROLINA G.; et al. GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil. Alzheimer Disease & Associated Disorders, v. 30, n. 4, p. 310-317, OCT-DEC 2016. (13/01758-4)