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

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

Autor Porto, Marianna Picarelli Ribeiro Autor UNIFESP Google Scholar
Vergani, Naja Autor UNIFESP Google Scholar
Carvalho, Antonio Carlos Autor UNIFESP Google Scholar
Cernach, Mirlene Cecilia Soares Pinho Autor UNIFESP Google Scholar
Brunoni, Decio Autor UNIFESP Google Scholar
Perez, Ana Beatriz Alvarez Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
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.
Palavra-chave Holt-Oram syndrome
congenital heart disease
TBX5 gene
GATA gene
NKX2.5 gene
mutation analysis
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Número do financiamento FAPESP: 03/01623-0
Data de publicação 2010-01-01
Publicado em Genetics and Molecular Biology. Sociedade Brasileira de Genética, v. 33, n. 2, p. 232-236, 2010.
ISSN 1415-4757 (Sherpa/Romeo, fator de impacto)
Publicador Sociedade Brasileira de Genética
Extensão 232-236
Fonte http://dx.doi.org/10.1590/S1415-47572010005000051
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000278958700006
SciELO S1415-47572010000200006 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/5543

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