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

Autores
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.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Materia
Cbs
Cognition
Ftd
Mapt
P301l
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/46982
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/46982
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South AmericaGatto, Emilia MabelAllegri, Ricardo FranciscoDa Prat, GustavoChrem Mendez, Patricio AlexisHanna, David S.Dorschner, Michael O.Surace, Ezequiel IgnacioZabetian, Cyrus P.Mata, Ignacio F.CbsCognitionFtdMaptP301lhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Frontotemporal 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; ArgentinaFil: 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; ColombiaFil: Da Prat, Gustavo. Fundación Mundo Sano. Instituto de Neurociencias Bs.As.; ArgentinaFil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Hanna, David S.. University of Washington; Estados UnidosFil: Dorschner, Michael O.. University of Washington; Estados UnidosFil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Zabetian, Cyrus P.. Geriatric Research Education and Clinical Center; Estados Unidos. University of Washington; Estados UnidosFil: Mata, Ignacio F.. Geriatric Research Education and Clinical Center; Estados Unidos. University of Washington; Estados UnidosElsevier Science Inc2016-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46982Gatto, Emilia Mabel; Allegri, Ricardo Francisco; Da Prat, Gustavo; Chrem Mendez, Patricio Alexis; Hanna, David S.; et al.; Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America; Elsevier Science Inc; Neurobiology of Aging; 53; 12-2016; 195.e11-195.e170197-4580CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neurobiolaging.2017.02.002info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0197458017300374info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385275/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:09:44Zoai:ri.conicet.gov.ar:11336/46982instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:09:44.398CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
title Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
spellingShingle Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
Gatto, Emilia Mabel
Cbs
Cognition
Ftd
Mapt
P301l
title_short Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
title_full Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
title_fullStr Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
title_full_unstemmed Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
title_sort Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America
dc.creator.none.fl_str_mv 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.
author Gatto, Emilia Mabel
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cbs
Cognition
Ftd
Mapt
P301l
topic Cbs
Cognition
Ftd
Mapt
P301l
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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
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.
publishDate 2016
dc.date.none.fl_str_mv 2016-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/46982
Gatto, Emilia Mabel; Allegri, Ricardo Francisco; Da Prat, Gustavo; Chrem Mendez, Patricio Alexis; Hanna, David S.; et al.; Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America; Elsevier Science Inc; Neurobiology of Aging; 53; 12-2016; 195.e11-195.e17
0197-4580
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46982
identifier_str_mv Gatto, Emilia Mabel; Allegri, Ricardo Francisco; Da Prat, Gustavo; Chrem Mendez, Patricio Alexis; Hanna, David S.; et al.; Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America; Elsevier Science Inc; Neurobiology of Aging; 53; 12-2016; 195.e11-195.e17
0197-4580
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neurobiolaging.2017.02.002
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0197458017300374
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385275/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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