GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil

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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. ; Smid, Jerusa ; Nascimento, Camila F. ; Grinberg, Lea T. ; Brucki, Sonia M. D. ; Maximino, Jessica R. ; Camargos, Sarah T. ; Chadi, Gerson ; Caramelli, Paulo ; Nitrini, Ricardo

• Document type: Journal article
• Source: Alzheimer Disease & Associated Disorders; v. 30, n. 4, p. 310-317, OCT-DEC 2016.
• Web of Science Citations: 3

Abstract

Background: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. Objective: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. Methods: We included 76 probands diagnosed with behavioral-variant FTD (n = 55), semantic-variant Primary Progressive Aphasia (PPA) (n = 11), or nonfluent-variant PPA (n = 10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. Results: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs{*}12, and p.K259Afs{*}23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. Conclusions: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%. (AU)

• FAPESP's process: 13/01758-4 - Screening for mutations in GRN and MAPT and measurement of plasma progranulin in a Brazilian cohort of patients with frontotemporal lobar degeneration
• Grantee: Ricardo Nitrini
• Support Opportunities: Regular Research Grants