C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients

A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD p...

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Autores: Dobson-Stone, Carol, Hallupp, Marianne, Loy, Clement T., Thompson, Elizabeth M., Haan, Eric, Sue, Carolyn M., Panegyres, Peter K., Razquin, Cristina, Seijo Martínez, Manuel, Reñé Ramírez, Ramon, Gascón-Bayarri, Jordi, Campdelacreu i Fumadó, Jaume, Schmoll, Birgit, Volk, Alexander E., Brooks, William S., Schofield, Peter R., Pastor, Pau, Kwok, John B. J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/126470
Acceso en línea:https://hdl.handle.net/2445/126470
Access Level:acceso abierto
Palabra clave:Demència
Esclerosi lateral amiotròfica
Dementia
Amyotrophic lateral sclerosis
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spelling C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia PatientsDobson-Stone, CarolHallupp, MarianneLoy, Clement T.Thompson, Elizabeth M.Haan, EricSue, Carolyn M.Panegyres, Peter K.Razquin, CristinaSeijo Martínez, ManuelReñé Ramírez, RamonGascón-Bayarri, JordiCampdelacreu i Fumadó, JaumeSchmoll, BirgitVolk, Alexander E.Brooks, William S.Schofield, Peter R.Pastor, PauKwok, John B. J.DemènciaEsclerosi lateral amiotròficaDementiaAmyotrophic lateral sclerosisA hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only similar to 65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as similar to 65 repeats may be sufficient to cause disease.Public Library of Science (PLoS)2018201820132018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion6 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/126470Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0056899PLoS One, 2013, vol. 8, num. 2, p. e56899https://doi.org/10.1371/journal.pone.0056899cc by (c) Dobson-Stone et al., 2013http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1264702026-05-29T05:05:01Z
dc.title.none.fl_str_mv C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
title C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
spellingShingle C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
Dobson-Stone, Carol
Demència
Esclerosi lateral amiotròfica
Dementia
Amyotrophic lateral sclerosis
title_short C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
title_full C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
title_fullStr C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
title_full_unstemmed C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
title_sort C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients
dc.creator.none.fl_str_mv Dobson-Stone, Carol
Hallupp, Marianne
Loy, Clement T.
Thompson, Elizabeth M.
Haan, Eric
Sue, Carolyn M.
Panegyres, Peter K.
Razquin, Cristina
Seijo Martínez, Manuel
Reñé Ramírez, Ramon
Gascón-Bayarri, Jordi
Campdelacreu i Fumadó, Jaume
Schmoll, Birgit
Volk, Alexander E.
Brooks, William S.
Schofield, Peter R.
Pastor, Pau
Kwok, John B. J.
author Dobson-Stone, Carol
author_facet Dobson-Stone, Carol
Hallupp, Marianne
Loy, Clement T.
Thompson, Elizabeth M.
Haan, Eric
Sue, Carolyn M.
Panegyres, Peter K.
Razquin, Cristina
Seijo Martínez, Manuel
Reñé Ramírez, Ramon
Gascón-Bayarri, Jordi
Campdelacreu i Fumadó, Jaume
Schmoll, Birgit
Volk, Alexander E.
Brooks, William S.
Schofield, Peter R.
Pastor, Pau
Kwok, John B. J.
author_role author
author2 Hallupp, Marianne
Loy, Clement T.
Thompson, Elizabeth M.
Haan, Eric
Sue, Carolyn M.
Panegyres, Peter K.
Razquin, Cristina
Seijo Martínez, Manuel
Reñé Ramírez, Ramon
Gascón-Bayarri, Jordi
Campdelacreu i Fumadó, Jaume
Schmoll, Birgit
Volk, Alexander E.
Brooks, William S.
Schofield, Peter R.
Pastor, Pau
Kwok, John B. J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Demència
Esclerosi lateral amiotròfica
Dementia
Amyotrophic lateral sclerosis
topic Demència
Esclerosi lateral amiotròfica
Dementia
Amyotrophic lateral sclerosis
description A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only similar to 65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as similar to 65 repeats may be sufficient to cause disease.
publishDate 2013
dc.date.none.fl_str_mv 2013
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126470
url https://hdl.handle.net/2445/126470
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0056899
PLoS One, 2013, vol. 8, num. 2, p. e56899
https://doi.org/10.1371/journal.pone.0056899
dc.rights.none.fl_str_mv cc by (c) Dobson-Stone et al., 2013
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Dobson-Stone et al., 2013
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 6 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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