Plakoglobin (JUP) gene and Arrhythmogenic Cardiomyopathy (ACM)
The Junction Plakoglobin (JUP) gene encodes for the protein plakoglobin, found in cells of the heart and skin where it is part of adherens junctions and desmosomes which help to hold neighboring cells together. It also plays a role in cell signaling within the Wnt pathway involved in the normal development of the heart, skin, and hair.12 Naxos disease, a cardio-cutaneous syndrome, is an autosomal recessive condition involving a two base-pair deletion of plakoglobin, characterized by effects on the heart (ARVC), skin (palmoplantar keratosis) and hair (woolly hair).13 The first case of isolated ARVC without cutaneous manifestations came from the only known autosomal dominant mutation in JUP which was reported in a proband in Germany in 2007. This mutation came from a three base pair insertion causing an addition of a terminal serine residue in the plakoglobin gene which affects the stability and degradation of plakoglobin.14 In contrast, a rare but severe phenotype associated with a homozygous JUP mutation with complete loss of plakoglobin can cause diffuse skin erosion, a condition referred to as lethal congenital epidermolysis bullosa (LECEB).15Of note, our patient, in contrast, was found to have an isolated (heterozygous) JUP gene mutation, and appears to have manifested much less severe phenotype, particularly without the manifestation of any cutaneous symptoms. Moreover, to date, there has not been any published cases on left sided or biventricular dysfunction or fibrosis in patients with an isolated plakoglobin mutation.