Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum

Background: Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50-60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present...

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Autores: López M, García-Oguiza A, Armstrong J, García-Cobaleda I, García-Miñaur S, Santos-Simarro F, Seidel V, Domínguez-Garrido E
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p13906
Acesso em linha:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13906
Access Level:acceso abierto
Palavra-chave:RSTS
EP300-Rubinstein-Taybi
Broad thumbs
Intellectual disability
EP300-mutations
EP300-RSTS-phenotype
EP300
RSTS-2
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spelling Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrumLópez MGarcía-Oguiza AArmstrong JGarcía-Cobaleda IGarcía-Miñaur SSantos-Simarro FSeidel VDomínguez-Garrido ERSTSEP300-Rubinstein-TaybiBroad thumbsIntellectual disabilityEP300-mutationsEP300-RSTS-phenotypeEP300RSTS-2Background: Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50-60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present the clinical and molecular characterization of a cohort of RSTS patients carrying EP300 mutations. Methods: Patients were selected from a cohort of 72 individuals suspected of RSTS after being negative in CREBBP study. MLPA and panel-based NGS EP300 were performed. Results: Eight patients were found to carry EP300 mutations. Phenotypic characteristics included: intellectual disability (generally mild), postnatal growth retardation, infant feeding problems, psychomotor and language delay and typical facial dysmorphisms (microcephaly, downslanting palpebral fissures, columella below the alae nasi, and prominent nose). Broad thumbs and/or halluces were common, but angulated thumbs were only found in two patients. We identified across the gene novel mutations, including large deletion, frameshift mutations, nonsense, missense and splicing alterations, confirming de novo origin in all but one (the mother, possibly underdiagnosed, has short and broad thumbs and had learning difficulties). Conclusions: The clinical evaluation of our patients corroborates that clinical features in EP300 are less marked than in CREBBP patients although it is difficult to establish a genotype-phenotype correlation although. It is remarkable that these findings are observed in a RSTS-diagnosed cohort; some patients harbouring EP300 mutations could present a different phenotype. Broadening the knowledge about EP300-RSTS phenotype may contribute to improve the management of patients and the counselling to the families.BMC2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13906BMC Medical GeneticsISSN: 14712350reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p139062026-05-27T12:37:41Z
dc.title.none.fl_str_mv Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
title Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
spellingShingle Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
López M
RSTS
EP300-Rubinstein-Taybi
Broad thumbs
Intellectual disability
EP300-mutations
EP300-RSTS-phenotype
EP300
RSTS-2
title_short Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
title_full Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
title_fullStr Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
title_full_unstemmed Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
title_sort Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum
dc.creator.none.fl_str_mv López M
García-Oguiza A
Armstrong J
García-Cobaleda I
García-Miñaur S
Santos-Simarro F
Seidel V
Domínguez-Garrido E
author López M
author_facet López M
García-Oguiza A
Armstrong J
García-Cobaleda I
García-Miñaur S
Santos-Simarro F
Seidel V
Domínguez-Garrido E
author_role author
author2 García-Oguiza A
Armstrong J
García-Cobaleda I
García-Miñaur S
Santos-Simarro F
Seidel V
Domínguez-Garrido E
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RSTS
EP300-Rubinstein-Taybi
Broad thumbs
Intellectual disability
EP300-mutations
EP300-RSTS-phenotype
EP300
RSTS-2
topic RSTS
EP300-Rubinstein-Taybi
Broad thumbs
Intellectual disability
EP300-mutations
EP300-RSTS-phenotype
EP300
RSTS-2
description Background: Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50-60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present the clinical and molecular characterization of a cohort of RSTS patients carrying EP300 mutations. Methods: Patients were selected from a cohort of 72 individuals suspected of RSTS after being negative in CREBBP study. MLPA and panel-based NGS EP300 were performed. Results: Eight patients were found to carry EP300 mutations. Phenotypic characteristics included: intellectual disability (generally mild), postnatal growth retardation, infant feeding problems, psychomotor and language delay and typical facial dysmorphisms (microcephaly, downslanting palpebral fissures, columella below the alae nasi, and prominent nose). Broad thumbs and/or halluces were common, but angulated thumbs were only found in two patients. We identified across the gene novel mutations, including large deletion, frameshift mutations, nonsense, missense and splicing alterations, confirming de novo origin in all but one (the mother, possibly underdiagnosed, has short and broad thumbs and had learning difficulties). Conclusions: The clinical evaluation of our patients corroborates that clinical features in EP300 are less marked than in CREBBP patients although it is difficult to establish a genotype-phenotype correlation although. It is remarkable that these findings are observed in a RSTS-diagnosed cohort; some patients harbouring EP300 mutations could present a different phenotype. Broadening the knowledge about EP300-RSTS phenotype may contribute to improve the management of patients and the counselling to the families.
publishDate 2018
dc.date.none.fl_str_mv 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://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13906
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13906
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.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv BMC Medical Genetics
ISSN: 14712350
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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