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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/46982
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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 Técnicas2025-09-29T09:41:07Zoai: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:34982025-09-29 09:41:07.663CONICET 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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |