Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , |
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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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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1814268433063215104 |