Key result
Candidate gene screening in 64 ARVC/D probands without known desmosomal mutations yielded no variants in PKP2 3'-UTR, PNN, CTNNA3, CAV1, or PLN, but found rare PERP and PKP4 variants in 1 proband.
Observational (n=64)
Mutations in the studied candidate genes and regulation of PKP2 mRNA via 3'-UTR dependent mechanisms are unlikely to be major causes of ARVC/D in patients without known desmosomal mutations.
Negative screening argues against these candidates as major ARVC/D causes; leaves open other genetic contributors in desmosomal mutation-negative patients.
AIMS: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by fibro-fatty replacement of the right ventricle and ventricular arrhythmias. The major disease-causing genes encode cardiac desmosomal components but are involved in only ∼50% of patients. To identify the missing genetic determinants, we used a candidate gene approach, focusing on the 3'-untranslated region (UTR) of the main ARVC/D gene PKP2 and on additional genes involved in desmosomal structure or function. METHODS AND RESULTS: We screened a population of 64 ARVC/D probands with no identified mutations in any of the five known desmosomal genes (PKP2, DSG2, DSP, DSC2, and JUP). No putative mutation was identified in the 3'-UTR of PKP2 or in PNN, CTNNA3, CAV1, or PLN coding sequences. In a single proband, we identified two rare heterozygous missense variants affecting evolutionary conserved residues: c.175G>A (p.Gly59Arg) in PERP and c.1811A>G (p.Asp604Gly) in PKP4 (minor allele frequency <0.5% in control population). CONCLUSION: Our study suggests that mutations in the candidate genes studied and regulation of PKP2 mRNA via 3'-UTR dependent mechanisms are unlikely to be major causes of ARVC/D in the studied population. Additional studies are needed to investigate the putative effects of rare PKP4 and PERP variants in this disease.
No takes yet. Share an insight, caveat, or question.
Gandjbakhch et al. (2013) conducted an observational in Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (n=64). Candidate gene screening was evaluated on Identification of putative mutations in candidate genes. Candidate gene screening in 64 ARVC/D probands without known desmosomal mutations yielded no variants in PKP2 3'-UTR, PNN, CTNNA3, CAV1, or PLN, but found rare PERP and PKP4 variants in 1 proband.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: