Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America

Authors
Gatto, Emilia Mabel; Allegri, Ricardo Francisco; Da Prat, Gustavo; Chrem Mendez, Patricio Alexis; Hanna, David S.; Dorschner, Michael O.; Surace, Ezequiel Ignacio; Zabetian, Cyrus P.; Mata, Ignacio F.
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and also in the genes coding for the protein associated with microtubule tau (MAPT) and progranulin (GRN) on chromosome 17 (FTDP-17). Herein, we report an Argentinean family, of Basque ancestry, with an extensive family history of behavioral variant of FTD. Twenty-one members over 6 generations composed the pedigree. An extensive neurologic and neurocognitive examination was performed on 2 symptomatic individuals and 3 nonsymptomatic individuals. Two different phenotypes were identified among affected members, CBS in the proband and FTD in his brother. DNA was extracted from blood for these 5 individuals and whole-exome sequencing was performed on 3 of them followed by Sanger sequencing of candidate genes on the other 2. In both affected individuals, a missense mutation (p.P301L; rs63751273) in exon 10 of the MAPT gene (chr17q21.3) was identified. Among MAPT mutations, p.P301L is the most frequently associated to different phenotypes: (1) aggressive, symmetrical, and early-onset Parkinsonism; (2) late parkinsonism associated with FTD; and (3) progressive supranuclear palsy but only exceptionally it is reported associated to CBS. This is the first report of the occurrence of the p.P301L-MAPT mutation in South America and supports the marked phenotypic heterogeneity among members of the same family as previously reported.
Fil: Gatto, Emilia Mabel. Fundación Mundo Sano. Instituto de Neurociencias Bs.As.; Argentina. Sanatorio de la Trinidad Mitre; Argentina
Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad de la Costa; Colombia
Fil: Da Prat, Gustavo. Fundación Mundo Sano. Instituto de Neurociencias Bs.As.; Argentina
Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Hanna, David S.. University of Washington; Estados Unidos
Fil: Dorschner, Michael O.. University of Washington; Estados Unidos
Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Zabetian, Cyrus P.. Geriatric Research Education and Clinical Center; Estados Unidos. University of Washington; Estados Unidos
Fil: Mata, Ignacio F.. Geriatric Research Education and Clinical Center; Estados Unidos. University of Washington; Estados Unidos
Subject
CBS
COGNITION
FTD
MAPT
P301L
Medicina Critica y de Emergencia
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/46982