Novel plakophilin2 mutation: three-generation family with arrhythmogenic right ventricular cardiomyopathy.
OBJECTIVE
The autosomal dominant form of arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to mutations in desmosomal proteins. A mutation in plakophilin 2 (PKP 2) is a frequent cause for ARVC. We describe a new mutation in the PKP2 gene, the genotype-phenotype variation in this mutation and its clinical consequences.


METHODS
Individuals in a three-generation family were investigated after the sudden cardiac death of a young male. Clinical evaluation, electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy and genetic testing were performed.


RESULTS
A novel heterozygote mutation, a c.368G > A transition, located in exon 3 of the PKP2 gene was found (p.Trp123X). The phenotype was characterized by arrhythmia at an early age in some individuals, with mild abnormalities on imaging.


CONCLUSIONS
This new plakophilin mutation demonstrates variable penetrance and phenotypic expression in ARVC, and highlights the need of genetic testing and thorough phenotype examination in ARVC pedigrees.
Department of Medical and Health Sciences, Division of Clinical Physiology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. meriam.astrom.aneq@lio.se
Meriam Åström
MÅ
Aneq
Christina
C
Fluur
Malin
M
Rehnberg
Peter
P
Söderkvist
Jan
J
Engvall
Eva
E
Nylander
Cecilia
C
Gunnarsson
D000293:Adolescent; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics*
C495337:PKP2 protein, human; D051191:Plakophilins