RATIONALE Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. OBJECTIVE The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for stu...

BACKGROUND The Holt-Oram syndrome (HOS) is an autosomal dominant disorder affecting 1/100.000 live births. It is defined by upper limb anomalies and congenital heart defects with variable severity. We describe a dramatic phenotype of a male, 15-month-old patient being investigated for strict diagnostic criteria of HOS. METHODS AND RESULTS Genetic analysis revealed a so far unpublished TBX5 mu...

Spontaneous self-terminating atrial fibrillation (AF) is one of the most common heart rhythm disorders, yet the regulatory molecular mechanisms underlying this syndrome are rather unclear. MicroRNA (miRNA) transcriptome and expression of candidate transcription factors (TFs) with potential roles in arrhythmogenesis, such as Pitx2, Tbx5, and myocardin (Myocd), were analyzed by microarray, qRT-PC...

Vertebrates have two pairs of morphologically distinct appendages, the forelimbs and the hindlimbs. Although the mechanisms necessary for limb outgrowth and polarity are becoming fairly well-understood little is known about how limb-type identity is regulated. The homeobox containing transcription factor Pitx1 expressed in hindlimb bud mesenchyme and has been shown to be involved in limb-type d...

The cardiac conduction system comprises a specialized tract of electrically coupled cardiomyocytes responsible for impulse propagation through the heart. Abnormalities in cardiac conduction are responsible for numerous forms of cardiac arrhythmias, but relatively little is known about the gene regulatory mechanisms that control the formation of the conduction system. We demonstrate that a dista...

Vertebrates have two pairs of morphologically distinct appendages, the forelimbs and the hindlimbs. Although the mechanisms necessary for limb outgrowth and polarity are becoming fairly well-understood little is known about how limb-type identity is regulated. The homeobox containing transcription factor Pitx1 expressed in hindlimb bud mesenchyme and has been shown to be involved in limb-type d...