Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome
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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Sociedade Brasileira de Genética
2010
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oai:scielo:S1415-475720100002000062010-06-14Novel mutations in the TBX5 gene in patients with Holt-Oram SyndromePorto,Marianna P.R.Vergani,NajaCarvalho,Antonio Carlos C.Cernach,Mirlene C.S.P.Brunoni,DecioPerez,Ana Beatriz A. Holt-Oram syndrome congenital heart disease TBX5 gene GATA gene NKX2.5 gene mutation analysis 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.info:eu-repo/semantics/openAccessSociedade Brasileira de GenéticaGenetics and Molecular Biology v.33 n.2 20102010-01-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200006en10.1590/S1415-47572010005000051 |
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Porto,Marianna P.R. Vergani,Naja Carvalho,Antonio Carlos C. Cernach,Mirlene C.S.P. Brunoni,Decio Perez,Ana Beatriz A. |
spellingShingle |
Porto,Marianna P.R. Vergani,Naja Carvalho,Antonio Carlos C. Cernach,Mirlene C.S.P. Brunoni,Decio Perez,Ana Beatriz A. Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome |
author_facet |
Porto,Marianna P.R. Vergani,Naja Carvalho,Antonio Carlos C. Cernach,Mirlene C.S.P. Brunoni,Decio Perez,Ana Beatriz A. |
author_sort |
Porto,Marianna P.R. |
title |
Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome |
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 |
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. |
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Sociedade Brasileira de Genética |
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2010 |
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http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200006 |
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