Molecular study
Whole-Exome sequencing trio was conducted in Centogene lab, Rostock, Germany including both parents and the baby DNAs after obtaining consents. The study detected two variants in the PKP2 gene. The first variant c.1688+1G>A is predicted to disrupt the highly conserved donor splice site of exon 7 inherited from the father. According to HGMD Professional 2018.2, this variant has previously been described as disease causing for arrhythmogenic right ventricular dysplasia/cardiomyopathy by Fressart et al., 2010 (PMID: 20400443). ClinVar lists this variant as pathogenic and likely pathogenic (clinical testing, Variation ID: 45038). The second PKP2 variant c.2274del p(Asn759Ilefs*41) creates a shift in the reading frame starting at codon 759 inherited from the mother. The new reading frame ends in a stop codon 40 positions downstream. ClinVar lists this variant as likely pathogenic (clinical testing, Variation ID: 202023). Furthermore, in Centogene’s mutation database (CentoMD®5.0), this variant was previously detected in a patient with an overlapping phenotype in a homozygous state (figure 3). Neither of the two variants was detected in two older healthy siblings.
Cardiac evaluation including EKG and echocardiogram the asymptomatic parents was unremarkable.
.