Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome

Detalhes bibliográficos
Autor(a) principal: Porto, Marianna Picarelli Ribeiro [UNIFESP]
Data de Publicação: 2010
Outros Autores: Vergani, Naja [UNIFESP], Carvalho, Antonio Carlos [UNIFESP], Cernach, Mirlene Cecilia Soares Pinho [UNIFESP], Brunoni, Decio [UNIFESP], Perez, Ana Beatriz Alvarez [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1590/S1415-47572010005000051
http://repositorio.unifesp.br/handle/11600/5543
Resumo: The Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father.
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spelling Novel mutations in the TBX5 gene in patients with Holt-Oram SyndromeHolt-Oram syndromecongenital heart diseaseTBX5 geneGATA geneNKX2.5 genemutation analysisThe Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father.Universidade Federal de São Paulo (UNIFESP) Department of MorfologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP, Department of MorfologiaUNIFESP, Depto. de MedicinaSciELOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 03/01623-0Sociedade Brasileira de GenéticaUniversidade Federal de São Paulo (UNIFESP)Porto, Marianna Picarelli Ribeiro [UNIFESP]Vergani, Naja [UNIFESP]Carvalho, Antonio Carlos [UNIFESP]Cernach, Mirlene Cecilia Soares Pinho [UNIFESP]Brunoni, Decio [UNIFESP]Perez, Ana Beatriz Alvarez [UNIFESP]2015-06-14T13:41:29Z2015-06-14T13:41:29Z2010-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion232-236application/pdfhttp://dx.doi.org/10.1590/S1415-47572010005000051Genetics and Molecular Biology. Sociedade Brasileira de Genética, v. 33, n. 2, p. 232-236, 2010.10.1590/S1415-47572010005000051S1415-47572010000200006.pdf1415-4757S1415-47572010000200006http://repositorio.unifesp.br/handle/11600/5543WOS:000278958700006engGenetics and Molecular Biologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-06T06:06:01Zoai:repositorio.unifesp.br/:11600/5543Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-06T06:06:01Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
title Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
spellingShingle Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
Porto, Marianna Picarelli Ribeiro [UNIFESP]
Holt-Oram syndrome
congenital heart disease
TBX5 gene
GATA gene
NKX2.5 gene
mutation analysis
title_short Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
title_full Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
title_fullStr Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
title_full_unstemmed Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
title_sort Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
author Porto, Marianna Picarelli Ribeiro [UNIFESP]
author_facet Porto, Marianna Picarelli Ribeiro [UNIFESP]
Vergani, Naja [UNIFESP]
Carvalho, Antonio Carlos [UNIFESP]
Cernach, Mirlene Cecilia Soares Pinho [UNIFESP]
Brunoni, Decio [UNIFESP]
Perez, Ana Beatriz Alvarez [UNIFESP]
author_role author
author2 Vergani, Naja [UNIFESP]
Carvalho, Antonio Carlos [UNIFESP]
Cernach, Mirlene Cecilia Soares Pinho [UNIFESP]
Brunoni, Decio [UNIFESP]
Perez, Ana Beatriz Alvarez [UNIFESP]
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Porto, Marianna Picarelli Ribeiro [UNIFESP]
Vergani, Naja [UNIFESP]
Carvalho, Antonio Carlos [UNIFESP]
Cernach, Mirlene Cecilia Soares Pinho [UNIFESP]
Brunoni, Decio [UNIFESP]
Perez, Ana Beatriz Alvarez [UNIFESP]
dc.subject.por.fl_str_mv Holt-Oram syndrome
congenital heart disease
TBX5 gene
GATA gene
NKX2.5 gene
mutation analysis
topic Holt-Oram syndrome
congenital heart disease
TBX5 gene
GATA gene
NKX2.5 gene
mutation analysis
description The Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father.
publishDate 2010
dc.date.none.fl_str_mv 2010-01-01
2015-06-14T13:41:29Z
2015-06-14T13:41:29Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1590/S1415-47572010005000051
Genetics and Molecular Biology. Sociedade Brasileira de Genética, v. 33, n. 2, p. 232-236, 2010.
10.1590/S1415-47572010005000051
S1415-47572010000200006.pdf
1415-4757
S1415-47572010000200006
http://repositorio.unifesp.br/handle/11600/5543
WOS:000278958700006
url http://dx.doi.org/10.1590/S1415-47572010005000051
http://repositorio.unifesp.br/handle/11600/5543
identifier_str_mv Genetics and Molecular Biology. Sociedade Brasileira de Genética, v. 33, n. 2, p. 232-236, 2010.
10.1590/S1415-47572010005000051
S1415-47572010000200006.pdf
1415-4757
S1415-47572010000200006
WOS:000278958700006
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Genetics and Molecular Biology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 232-236
application/pdf
dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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