Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma

Autores
Ottaviani, Daniela; Parma, Diana Lidia; Giliberto, Florencia; Ferrer, Marcela Maria; Fandino, Adriana; Davila, María Teresa; Chantada, Guillermo Luis; Szijan, Irena
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. Methods: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of “at risk haplotypes” and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. Results: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. Conclusion: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.
Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Davila, María Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
At-Risk Haplotype
Genotype-Phenotype Correlation
Penetrance
Rb1 Mutations
Rb1 Tumor Suppressor Gene
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:11336/16507
Acceder
id CONICETDig_07ad10a100877ec73336b9faf5d15a12
oai_identifier_str oai:ri.conicet.gov.ar:11336/16507
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastomaOttaviani, DanielaParma, Diana LidiaGiliberto, FlorenciaFerrer, Marcela MariaFandino, AdrianaDavila, María TeresaChantada, Guillermo LuisSzijan, IrenaAt-Risk HaplotypeGenotype-Phenotype CorrelationPenetranceRb1 MutationsRb1 Tumor Suppressor Genehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. Methods: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of “at risk haplotypes” and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. Results: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. Conclusion: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Davila, María Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaTaylor & Francis2013-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16507Ottaviani, Daniela; Parma, Diana Lidia; Giliberto, Florencia; Ferrer, Marcela Maria; Fandino, Adriana; et al.; Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma; Taylor & Francis; Ophthalmic Genetics; 34; 4; 1-2013; 189-1981381-68101744-5094enginfo:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/13816810.2012.755553info:eu-repo/semantics/altIdentifier/doi/10.3109/13816810.2012.755553info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:37Zoai:ri.conicet.gov.ar:11336/16507instacron: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:34982025-09-03 09:43:37.966CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
title Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
spellingShingle Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
Ottaviani, Daniela
At-Risk Haplotype
Genotype-Phenotype Correlation
Penetrance
Rb1 Mutations
Rb1 Tumor Suppressor Gene
title_short Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
title_full Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
title_fullStr Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
title_full_unstemmed Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
title_sort Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma
dc.creator.none.fl_str_mv Ottaviani, Daniela
Parma, Diana Lidia
Giliberto, Florencia
Ferrer, Marcela Maria
Fandino, Adriana
Davila, María Teresa
Chantada, Guillermo Luis
Szijan, Irena
author Ottaviani, Daniela
author_facet Ottaviani, Daniela
Parma, Diana Lidia
Giliberto, Florencia
Ferrer, Marcela Maria
Fandino, Adriana
Davila, María Teresa
Chantada, Guillermo Luis
Szijan, Irena
author_role author
author2 Parma, Diana Lidia
Giliberto, Florencia
Ferrer, Marcela Maria
Fandino, Adriana
Davila, María Teresa
Chantada, Guillermo Luis
Szijan, Irena
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv At-Risk Haplotype
Genotype-Phenotype Correlation
Penetrance
Rb1 Mutations
Rb1 Tumor Suppressor Gene
topic At-Risk Haplotype
Genotype-Phenotype Correlation
Penetrance
Rb1 Mutations
Rb1 Tumor Suppressor Gene
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. Methods: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of “at risk haplotypes” and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. Results: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. Conclusion: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.
Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Davila, María Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. Methods: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of “at risk haplotypes” and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. Results: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. Conclusion: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.
publishDate 2013
dc.date.none.fl_str_mv 2013-01
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/11336/16507
Ottaviani, Daniela; Parma, Diana Lidia; Giliberto, Florencia; Ferrer, Marcela Maria; Fandino, Adriana; et al.; Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma; Taylor & Francis; Ophthalmic Genetics; 34; 4; 1-2013; 189-198
1381-6810
1744-5094
url http://hdl.handle.net/11336/16507
identifier_str_mv Ottaviani, Daniela; Parma, Diana Lidia; Giliberto, Florencia; Ferrer, Marcela Maria; Fandino, Adriana; et al.; Spectrum of RB1 mutations in Argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma; Taylor & Francis; Ophthalmic Genetics; 34; 4; 1-2013; 189-198
1381-6810
1744-5094
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/13816810.2012.755553
info:eu-repo/semantics/altIdentifier/doi/10.3109/13816810.2012.755553
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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
_version_ 1842268614600687616
score 13.13397

Publicaciones similares