In myocardial fibers, each attachment plaque is composed of five constitutive proteins, junctional plakoglobin, plakophilin-2
, desmoplakin, desmoglein-2, and desmocollin-2.
Roche-Molina et al., "Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated version of human plakophilin-2
," Journal of the American College of Cardiology, vol.
Nearly 50% of patients suffering from ARVD have mutations in genes which encode desmosomes components--desmoplakin, plakoglobin, plakophilin-2
, desmoglein-2, and desmocollin-2 .
The query [Plakophilins[MeSH] AND case reports[PT]] generated 2 distinct main findings: 1 concerned plakophilin-1 mutations that cause ectodermal dysplasia skin fragility syndrome, and 1 reported novel plakophilin-2
Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation 2006; 113: 1641-9.
Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Plakophilin-2 (PKP-2): Highest number of mutations have been reported in PKP-2 gene causing ARVD/C9 thus suggesting the plakophillin may be a frequent cause of the disease.
The clinical manifestations of the probands harbouring desmoplakin gene mutations are similar to patients with other ARVCs except that probands with DSP mutations are characterized by a high occurrence of sudden death even in the concealed phase (49), while individuals harbouring plakophilin-2 genes mutations express the disease earlier in life, as determined by age at first clinical manifestation and age at first arrhythmias (65).
Mutations in the plakophilin-2 genes cause the disease affecting predominantly the RV, while desmocollin-2 gene mutations may be more frequently associated with left ventricular phenotype without significant right ventricular involvement (55).
Probands with TGF/3-3 gene mutation presented only non sustained ventricular tachycardia/ arrhythmias while probands carrying the mutation in the either desmoplakin or plakophilin-2 genes presented with all the four types--sustained ventricular tachycardia, non sustained VT (NVST), polymorphic ventricular complexes (PVCs) and ventricular fibrillation.
"Connexin 43 and plakophilin-2
as a protein complex that regulates blood-testis barrier dynamics," Proceedings of the National Academy of Sciences of the United States of America 106(25): 10213-10218.