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 ...

Effects of Eight Weeks High-Intensity Interval Training on the Expression Nkx2.5 and Tbx5 Genes in Heart Tissue Type 2 Male Diabetic Rats

Mutations in the Tbx5 transcription factor cause heart septal defects found in human Holt-Oram Syndrome. The complete extent to which Tbx5 functions in heart development, however, has not been established. Here we show that, in Xenopus embryos, Tbx5 is expressed in the early heart field, posterior to the cardiac homeobox transcription factor, Nkx2.5. During morphogenesis, Tbx5 is expressed thro...

Limb-type-specific expression of Tbx5/Tbx4 plays a key role in drawing distinction between a forelimb and a hindlimb. Here, we show insights into specification and determination during commitment of limb-type identity, in particular that median tissues regulate Tbx expressions. By using the RT-PCR technique on chick embryos, the onset of specific Tbx5/Tbx4 expression in the wing/leg region was ...

Background.  Variants of several genes encoding transcription modulators, signal transduction, and structural proteins are known to cause Mendelian congenital heart disease (CHD). NKX2-5 and GATA4 were the first CHD-causing genes identified by linkage analysis in large affected families. Mutations of TBX5 cause Holt-Oram syndrome, which includes CHD as a clinical feature. All three genes have a...

AIMS Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in catecholamine biosynthesis. Whereas the neuroendocrine roles of cathecolamines postnatally are well known, the presence and function of TH in organogenesis is unclear. The aim of this study was to define the expression of TH during cardiac development and to unravel the role it may play in heart formation. METHODS AND RES...

Normal development of the respiratory system is essential for survival and is regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes are known to be required in the epithelium, only Fgfs have been well studied in the mesenchyme. In this study, we investigated the roles of Tbx...

EDITOR—Although point mutations are responsible for many genetic disorders, it is increasingly being appreciated that many disorders can be caused by deletion or duplication of DNA sequences. Alterations in DNA copy number are responsible for several categories of disorders and can range in scale from a chromosome or chromosomal region to just one exon of a single gene. For instance, duplicatio...

Cardiac conduction system (CCS) disease, which results in disrupted conduction and impaired cardiac rhythm, is common with significant morbidity and mortality. Current treatment options are limited, and rational efforts to develop cell-based and regenerative therapies require knowledge of the molecular networks that establish and maintain CCS function. Recent genome-wide association studies (GW...