Search

Mutations in the αB-crystallin gene ( CRYAB) have been reported in desmin-related myopathies, with or without cardiac involvement. Mutations in this gene have also been documented in large multi-generation families with autosomal dominant congenital posterior pole cataract (CPPC). In these congenital cataract families no cardiac or muscular phenotype was reported. This report describes a family with an unusual read-through mutation in CRYAB, leading to the elongation of the normal αB-crystallin protein with 19 amino acid residues. Affected family members combine a CPPC with an adult onset dilated cardiomyopathy ( DCM), thereby expanding the αB-crystallinopathy phenotype. Repolarisation abnormalities preceded the onset of cardiomyopathy and were already present in childhood. No skeletal myopathy was observed. This report illustrates that congenital cataract can be a prelude to more severe disease even outside the context of inborn errors of metabolism. The identification of a CRYAB mutation in this family supports the notion that mutations in this gene are a rare cause of genetically determined DCM. The combined congenital cataract/cardiomyopathy phenotype adds to our understanding of the complex phenotypic spectrum of αB-crystallinopathies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Can we predict clinical response to cardiac resynchronization therapy by acute hemodynamic testing?," by B. W. L. De Boeck and colleagues is presented.

An abstract of the study " Heart failure in elderly "COPD" patients: an underestimated phenomenon," by F. H. Rutten and colleagues, is presented.

Abstract Objectives: The proarrhythmic early afterdepolarizations (EADs) during phase-2 of the cardiac action potential (phase-2 EADs) are associated with secondary Ca[sup 2+] -release of the sarcoplasmic reticulum. This makes it probable that the Ca[sup 2+] -activated Cl[sup -] current [I[sub Cl(Ca)] ] is present during phase-2 EADs. Activation of I[sub Cl(Ca)] during phase-2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase-2 EADs. The present study was designed to test this hypothesis. Methods and Results: The contribution of I[sub Cl(Ca)] during phase-2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch-clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 μ m noradrenaline. In sheep myocytes, the I[sub Cl(Ca)] blocker 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS, 0.5 mm) abolished phase-1 repolarization of the action potential in all myocytes tested. This indicates that I[sub Cl(Ca)] is present in all sheep myocytes. However, DIDS had no effect on phase-2 EAD characteristics. In human myocytes, DIDS neither affected phase-1 repolarization nor phase-2 EAD characteristics. Conclusion: In sheep ventricular myocytes, but not in human ventricular myocytes, I[sub Cl(Ca)] contributes to phase-1 repolarization of the action potential. In both sheep and human myocytes, I[sub Cl(Ca)] plays a limited role during phase-2 EADs. [ABSTRACT FROM AUTHOR]