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.