TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical Holt-Oram syndrome

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A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation.

Holt-Oram syndrome (HOS) is a heart/hand syndrome clinically characterized by upper limb and cardiac malformations. Mutations in T-box transcription factor 5 (TBX5) underlie this syndrome. Here, we describe a large atypical HOS family in which affected patients have mild skeletal deformations and paroxysmal atrial fibrillation, but few have congenital heart disease. Sequencing of TBX5 revealed ...

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Atrial Fibrillation and Other Clinical Manifestations of Altered TBX5 Dosage in Typical Holt-Oram Syndrome.

Atrial Fibrillation and Other Clinical Manifestations of Altered TBX5 Dosage in Typical Holt–Oram Syndrome To the editor: We were pleased to read the recent study in Circulation Research by Postma et al1 that describes an activation mutation in TBX5 that causes Holt–Oram syndrome. These exciting findings validate prior studies (reviewed elsewhere2) showing that cytogenetic abnormalities that pr...

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Holt-oram syndrome and atrial fibrillation: opening the (T)-box.

Cardiogenesis is a complex phenomenon: its success— and ultimately life births—depends on factors acting in a combinatorial or hierarchical fashion and turning on and off gene transcription. Actually, the incidence of cardiac defects at birth is relatively high (1% to 2%), and our comprehension of these phenomena very limited. Hence, the role of transcription factors in cardiac specification an...

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Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome.

The Holt-Oram syndrome (OMIM 142900) is an autosomal dominant disorder with clinical features characterised by a variety of skeletal malformations and congenital heart defects. The gene for Holt-Oram syndrome has been identified as TBX5 on chromosome 12q24. TBX5 encodes a protein of 518 amino acids that belongs to the family of the T box transcriptional factors, 11 and is expressed in embryonic...

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The mutation spectrum in Holt-Oram syndrome.

EDITOR—Holt-Oram syndrome (HOS) is a developmental disorder characterised by malformations of the radial ray of the forelimb and by congenital heart disease. The syndrome shows a marked variability in phenotype, with radial ray defects ranging from minor thumb abnormality through to severe reduction defect or phocomelia. The cardiac manifestations of HOS are similarly varied, and patients can p...

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ژورنال

عنوان ژورنال: Molecular Medicine Reports

سال: 2016

ISSN: 1791-2997,1791-3004

DOI: 10.3892/mmr.2016.5043