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

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

Author 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
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords Holt-Oram syndrome
congenital heart disease
TBX5 gene
GATA gene
NKX2.5 gene
mutation analysis
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 03/01623-0
Date 2010-01-01
Published in Genetics and Molecular Biology. Sociedade Brasileira de Genética, v. 33, n. 2, p. 232-236, 2010.
ISSN 1415-4757 (Sherpa/Romeo, impact factor)
Publisher Sociedade Brasileira de Genética
Extent 232-236
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000278958700006
SciELO ID S1415-47572010000200006 (statistics in SciELO)

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