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.
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