Mechanotransduction Going Wrong
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- arrhythmogenic cardiomyopathy
- dilated cardiomyopathy
- sudden cardiac death
Article, see p 1595
Arrhythmogenic cardiomyopathy (AC) is a genetic disorder characterized by high risk of life-threatening ventricular arrhythmias, sudden cardiac death, and progressive heart failure. Currently, there is evidence that AC includes a spectrum of cardiomyopathy phenotypes, ranging from the classical form of arrhythmogenic right ventricular cardiomyopathy (ARVC) to more recently identified forms of arrhythmogenic left ventricular cardiomyopathy.1,2
ARVC is considered a disease of the desmosome, because in the majority of cases, it is caused by mutations in genes encoding proteins of the cardiac desmosomes.3 However, mutations in nondesmosomal genes have also been found in ARVC, such as the genes encoding the cardiac ryanodine receptor 2 (RYR2), the transforming growth factor β-3 (TGFB3), the nuclear transmembrane protein 43 (TMEM43), and desmin (DES). Mutations in LMNA, encoding the nuclear envelope protein lamin A/C, known to cause dilated cardiomyopathy with an arrhythmic phenotype, was reported to cause also an ARVC phenotype,3 even though the association between LMNA and ARVC is still questioned.
In the left dominant form, which clinically presents as an arrhythmogenic dilated cardiomyopathy, the same desmosomal genes causing ARVC can be found,1 as well as LMNA and the more recently identified filamin C gene (FLNC), encoding an actin …