Original Research Article
Frontotemporal Dementia Caused by the P301L Mutation in the MAPT Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, SpainBorrego-Écija S.a · Morgado J.a, g · Palencia-Madrid L.b · Grau-Rivera O.c · Reñé R.d · Hernández I.e · Almenar C.f · Balasa M.a, h · Antonell A.a · Molinuevo J.L.a · Lladó A.a · Martínez de Pancorbo M.b · Gelpi E.c · Sánchez-Valle R.a, c
aAlzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, bBIOMICs Research Group, Lascaray Research Center, University of the Basque Country, Vitoria-Gasteiz, cNeurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, Barcelona, dNeurology Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, eMemory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, and fHospital Benito Menni CASM Germanes Hospitalaries, Sant Boi de Llobregat, Barcelona, Spain; gNeurology Department, Centro Hospitalar Lisboa Central, Lisboa, Portugal; hGlobal Brain Health Institute, Trinity College Dublin, Dublin, Ireland
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Background/Aims: We identified and studied 13 patients carrying the P301L mutation in the MAPT gene from the same area (Baix Llobregat County) in Barcelona, Spain. Methods: The demographic and clinical features were reviewed retrospectively. Detailed neuropathological characterization was obtained in 9 subjects. To investigate the origin of the P301L mutation in these families, 20 single nucleotide polymorphisms (SNPs) in the MAPT gene were analyzed. Results: The mean age at disease onset was 51 years and the mean disease duration was 7 years. The most common initial symptoms were behavioral changes (54%), followed by language disturbances (31%) and memory loss (15%). 46% developed parkinsonism. Neuropathology showed an extensive neuronal and glial 4-repeat (4R) tauopathy with “mini-Pick”-like bodies in the dentate gyrus as the characteristic underlying pathology in all cases. In 1 subject, additional 4R globular glial inclusions were observed. All the mutation carriers showed the same haplotype for the SNPs analyzed, suggesting a common ancestor. Conclusion: These findings suggest a relative homogeneous clinicopathological phenotype in P301L MAPT mutation carriers in our series. This phenotype might help in the differential diagnosis from other tauopathies and be a morphological hint for genetic testing. The haplotype analysis results suggest a founder effect of the P301L mutation in this area.
© 2017 S. Karger AG, Basel
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