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The article presents a study which determined the mutation frequency in MYH11, ACTA2, TGΒRI, and TGFΒRII in a population of individuals with genetically mediated thoracic aortic aneurysm (TAA). Nine percent of patients had mutation in one of the genes analyzed while three percents had mutations in ACTA2. Analyses showed that the TGFΒ2;IIb activating mutations alter receptor function on TGFΒ2 signaling.

Aims: Auditory stimulus-induced long QT syndrome (LQTS) is almost exclusively linked to mutations in the hERG potassium channel, which generates the IKr ventricular repolarization current. Here, a young woman with prior episodes of auditory stimulus-induced syncope presented with LQTS and ventricular fibrillation (VF) with hypomagnesaemia and hypocalcaemia after completing a marathon, followed by subsequent VF with hypokalaemia. The patient was found to harbour a KCNE2 gene mutation encoding a T10M amino acid substitution in MiRP1, an ancillary subunit that co-assembles with and functionally modulates hERG. Other family members with the mutation were asymptomatic, and the proband had no mutations in hERG or other LQTS-linked cardiac ion channel genes. The T10M mutation was absent from 578 unrelated, ethnically matched control chromosomes analysed here and was previously described only once—in an LQTS patient—but not functionally characterized. [ABSTRACT FROM PUBLISHER]

Carney complex is a genetic condition in which affected individuals develop benign tumours in various tissues, including the heart. Most individuals with Carney complex have a mutation in the PRKAR1A gene, which encodes the regulatory R1α subunit of protein kinase A — a significant component of the cyclic-AMP signalling pathway. Genetically engineered mutant Prkar1a mouse models show an increased propensity to develop tumours, and have established a role for R1α in initiating tumour formation and, potentially, in maintaining cell proliferation. Ongoing investigations are exploring the intersection of R1α-dependent cell signalling with other gene products such as perinatal myosin, mutation of which can also cause cardiac myxomas. [ABSTRACT FROM AUTHOR]

The article presents an update on the management of cardiovascular disease (CVD), which is a major source of morbidity and mortality worldwide. It is said that scientists are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Monogenic disorders typically is responsible for a small proportion of the total CVD observed in the population.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor—site mutation in intron 5 (c.631-2A→G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and the creation of a downstream premature termination codon. Quantitative analysis of cardiac DSC2 expression in patient specimens revealed a marked reduction in the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electrondense midlines, and associated myocardial contractility defects. These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function. [ABSTRACT FROM AUTHOR]