The transcription factor Tbx5 is expressed in the developing heart, eyes and anterior appendages. Mutations in human TBX5 cause Holt-Oram syndrome, a condition characterized by heart and upper limb malformations. Tbx5-knockout mouse embryos have severely impaired forelimb and heart morphogenesis from the earliest stages of their development. However, zebrafish embryos with compromised tbx5 func...

OBJECTIVES The TBX5 gene, a member of the T-box family, is associated with congenital heart disease, electrocardiographic parameters, and development of atrial fibrillation in the general population. This study aimed to elucidate the role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly linked to TBX5-related pathologies. MATERIALS AND METHODS A sample population of ...

The development of vertebrate limb buds is triggered in the lateral plate mesoderm by a cascade of genes, including members of the Fgf and Wnt families, as well as the transcription factor tbx5. Fgf8, which is expressed in the intermediate mesoderm, is thought to initiate forelimb formation by activating wnt2b, which then induces the expression of tbx5 in the adjacent lateral plate mesoderm. Tb...

Congenital heart disease is the most common type of birth defect with an incidence of 1%. Previously, we described a point mutation in GATA4 that segregated with cardiac defects in a family with autosomal dominant disease. The mutation (G296S) exhibited biochemical deficits and disrupted a novel interaction between Gata4 and Tbx5. To determine if Gata4 and Tbx5 genetically interact in vivo, we ...

The limb- and heart-specific Tbx5 transcription factor coexpresses with and directly binds to the novel PDZ-LIM domain protein, LMP4. LMP4 is distributed in the cytoplasm associated with the actin cytoskeleton. In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and cytoplasm and, in a complex with LMP4, localizes to actin filaments. Nuclear and cytoplasmic Tbx5 distribution ...

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...

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 3...

H olt-Oram syndrome (HOS) (MIM 142900), first described by Holt and Oram in 1960, is characterised by malformations of the upper limbs involving mainly the pre-axial ray and variable cardiac defects, most of them septation defects. This autosomal dominant inherited condition occurs in approximately 1 in 100 000 live births and shows high penetrative and variable intrafamilial and interfamilial ...

Holt Oram Syndrome (HOS) falls in rare prevalence category with probability of 0.7 100,000 live births. It is a autosomal dominant multiple malformation syndrome characterized by abnormalities affecting hands, wrists, arms,congenital heart defects and/or conduction problems. Genetic mutations observed TBX5 gene attributed as the main cause HOS. Our patient his late 40s was diagnosed Syndrome. H...

Tight control over gene expression is essential for precision in embryonic development and acquisition of the regulatory elements responsible is the predominant driver for evolution of new structures. Tbx5 and Tbx4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the initiation of limb outgrowth. Evolution of regulatory elements that activate Tbx...