title: A novel variant in plakophilin-2 gene detected in a family with arrhythmogenic right ventricular cardiomyopathy.
abstract: OBJECTIVE
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of muscular fibers predominantly in the right ventricle and with ventricular arrhythmias as the main clinical manifestation. Mutations in several components of the desmosome genes have been identified and mutations of the plakophilin-2 (PKP-2) gene are a common cause of ARVC. The aim of this study is to investigate the correlation between genotype and phenotype in a family with a novel PKP-2 variant.
  
  
  RESULTS
  This study describes the clinical findings and genetic analysis in a family with ARVC. A part of the family has been followed clinically long term for up to 27 years. Two not previously reported PKP-2 variants (L506P and T526A) have been identified in this family. Even though all members of this family share the novel variant L506P, the clinical features, i.e., their phenotypes are different. The L506P variant is located in exon 7 and affects a highly conserved residue. The same amino acid, leucine, is present in all species evaluated, indicating a functional importance and the variant is predicted to be damaging. The novel L506P variant in the PKP-2 gene is thus a possible pathogenic alteration in the described family with ARVC. In contrast, the T526A variant is weakly conserved and predicted to be tolerated.
  
  
  CONCLUSIONS
  While many of the reported ARVC mutations are truncating mutations, the possibly damaging variant found in this family, is a missense alteration affecting a highly conserved residue 506 located in exon 7.
authors.affiliation: Department of Cardiology, Uppsala University, Uppsala, Sweden. bozena.zofia.ostrowska@akademiska.se
authors.forename: Bozena
authors.initials: B
authors.lastname: Ostrowska Dahlgren
authors.forename: Marie
authors.initials: M
authors.lastname: Allen
authors.forename: Anne-Cristine
authors.initials: AC
authors.lastname: Lindström
authors.forename: Mia
authors.initials: M
authors.lastname: Bjerke
authors.forename: Carina
authors.initials: C
authors.lastname: Blomström-Lundqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D051191:Plakophilins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins