RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database

[Background] Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in...

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Detalhes bibliográficos
Autores: Valverde, José R., Alonso García de la Rosa, Francisco Javier, Palacios, Itziar, Pestaña, Ángel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/3204
Acesso em linha:http://hdl.handle.net/10261/3204
Access Level:acceso abierto
Palavra-chave:Retinoblastoma
RB1 gene mutations
Database
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spelling RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable databaseValverde, José R.Alonso García de la Rosa, Francisco JavierPalacios, ItziarPestaña, ÁngelRetinoblastomaRB1 gene mutationsDatabase[Background] Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships.[Results] A searchable database (RBGMdb) has been constructed with 932 published RB1 mutations. The spectrum of these mutations has been analyzed with the following results: 1) the retinoblastoma protein is frequently inactivated by deletions and nonsense mutations while missense mutations are the main inactivating event in most genetic diseases. 2) Near 40% of RB1 gene mutations are recurrent and gather in sixteen hot points, including twelve nonsense, two missense and three splicing mutations. The remainder mutations are scattered along RB1, being most frequent in exons 9, 10, 14, 17, 18, 20, and 23. 3) The analysis of RB1 mutations by country of origin of the patients identifies two groups in which the incidence of nonsense and splicing mutations show differences extremely significant, and suggest the involvement of predisposing ethnic backgrounds. 4) A significant association between late age at diagnosis and splicing mutations in bilateral retinoblastoma patients suggests the occurrence of a delayed-onset genotype. 5) Most of the reported mutations in low-penetrance families fall in three groups: a) Mutations in regulatory sequences at the promoter resulting in low expression of a normal Rb; b) Missense and in-frame deletions affecting non-essential sequence motifs which result in a partial inactivation of Rb functions; c) Splicing mutations leading to the reduction of normal mRNA splicing or to alternative splicing involving either true oncogenic or defective (weak) alleles.[Conclusions] The analysis of RB1 gene mutations logged in the RBGMdb has shown relevant phenotype-genotype relationships and provided working hypothesis to ascertain mechanisms linking certain mutations to ethnicity, delayed onset of the disease and low-penetrance. Gene profiling of tumors will help to clarify the genetic background linked to ethnicity and variable expressivity or delayed onset phenotypes.Comunidad de Madrid, GR/SAL/0855/2004Peer reviewedBioMed Central200820082005info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersion406983 bytesapplication/pdfhttp://hdl.handle.net/10261/3204reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/32042026-05-22T06:33:51Z
dc.title.none.fl_str_mv RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
title RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
spellingShingle RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
Valverde, José R.
Retinoblastoma
RB1 gene mutations
Database
title_short RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
title_full RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
title_fullStr RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
title_full_unstemmed RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
title_sort RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
dc.creator.none.fl_str_mv Valverde, José R.
Alonso García de la Rosa, Francisco Javier
Palacios, Itziar
Pestaña, Ángel
author Valverde, José R.
author_facet Valverde, José R.
Alonso García de la Rosa, Francisco Javier
Palacios, Itziar
Pestaña, Ángel
author_role author
author2 Alonso García de la Rosa, Francisco Javier
Palacios, Itziar
Pestaña, Ángel
author2_role author
author
author
dc.subject.none.fl_str_mv Retinoblastoma
RB1 gene mutations
Database
topic Retinoblastoma
RB1 gene mutations
Database
description [Background] Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships.
publishDate 2005
dc.date.none.fl_str_mv 2005
2008
2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/3204
url http://hdl.handle.net/10261/3204
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 406983 bytes
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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