The avian and mammalian heart originates from two distinct embryonic regions: an early differentiating first heart field and a dorsomedially located second heart field. It remains largely unknown when and how these subdivisions of the heart field divide into regions with different fates. Here, we identify in the mouse a subpopulation of the first (crescent-forming) field marked by endothelin re...

Holt-Oram syndrome (HOS) features radial ray hypoplasia, heart defect and cardiac conduction impairment. Ulnar-mammary syndrome (UMS) characterizes congenital defects of the ulnar side of the upper limbs, underdevelopment of apocrine glands including hypoplasia and the dysfunction of mammary glands, hypogonadism and obesity. Inheritance of both conditions is autosomal dominant, mutations or del...

At the end of every heartbeat, cardiac myocytes must relax to allow filling of the heart. Impaired relaxation is a significant factor in heart failure, but all pathways regulating the cardiac relaxation apparatus are not known. Haploinsufficiency of the T-box transcription factor Tbx5 in mouse and man causes congenital heart defects (CHDs) as part of Holt-Oram syndrome (HOS). Here, we show that...

OBJECTIVE Islet-1 is an important transcription factor for cardiac development through mediating extensive interactions between DNA and proteins. The present study was to investigate the role of Islet-1 in regulating the expression of cardiac development-related transcription factors and mechanism. METHODS AND RESULTS The expression of Islet-1 and histone acetylases (HATs) subtype p300 was de...

Comparative evolutionary studies have greatly aided our understanding of how the heart develops. Two recent articles from Benoit Bruneau’s laboratory reveal the power of the so-called evo-devo approach and provide yet further details of development, both of the heart itself and of the cells that build it. Thanks to our many and varied primitive cousins, developmental biologists are gaining a go...

Recent studies have identified the genetic underpinnings of a growing number of diseases through targeted exome sequencing. However, this strategy ignores the large component of the genome that does not code for proteins, but is nonetheless biologically functional. To address the possible involvement of regulatory variation in congenital heart diseases (CHDs), we searched for regulatory mutatio...

The Holt–Oram syndrome or atriodigital dysplasia is an autosomal dominant disorder with near complete penetrance and variable expression, caused by mutations of the TBX5 gene (12q24.1), affecting one in 100 000 live births. 60% of cases are familial and 40% sporadic. We present the case of a 8 months old male patient presented with respiratory problem .Patient had characteristic right sided han...

Holt-Oram syndrome (HOS) is a developmental disorder inherited in an autosomal-dominant pattern. Affected organs are the heart and forelimbs with upper extremity skeletal defects and congenital heart malformation. In this study we present three cases of HOS in the same family. In one of these three individuals we detected a transition of C to T (CTG-GTT, V205V) in exon 7 of the TBX5 gene. This ...

We report on a Saudi infant with Holt-Oram syndrome caused by a de novo missense mutation of the TBX5 gene. The mutation (Thr72Lys) is novel and has not been previously reported. The cardiac and limb defects in our patient were both severe, and the infant also had micrognathia and cleft palate. Previously reported cases of the Holt-Oram syndrome caused by missense mutations were reviewed and th...