Figures & data
Figure 1. Pedigree of the RYR2 exon 3 deletion carriers. The proband (II-3) is indicated by the black arrow. Family members carrying the RYR2 exon 3 deletion are indicated in solid black. The members with unknown clinical and genetic background information are indicated by ?.
Figure 2. Rhythm strips of the proband and her daughter. A: Three lead rhythm strip (25 mm/s, 10 mm/mV) taken during exercise of the female proband (II-3), at age 29 years following presentation with exertional syncope. Two minutes into stage 1 of the Bruce protocol, there are runs of polymorphic ventricular ectopy and ventricular tachycardia interrupted with occasional sinus beats. B: 12 lead rhythm strip (25 mm/s, 10 mm/mV) taken during exercise of an asymptomatic 7-year-old daughter of the proband (III-3) in stage 3, 9 min into the Bruce protocol. Frequent left bundle branch, inferior axis monomorphic ventricular extra beats develop into bigeminy.
Figure 3. Copy number changes in chromosome 1q43 of the proband. DEVA software output showing a copy number change (deletion; 10 probes; log2ratio: –0.6726) localized to chromosome 1q43 (235,560,602-235,561,416; hg18 co-ordinates) for the proband (II-3).
Figure 4. PCR amplification of the region encompassing exon 3 of the RYR2 gene. A: Amplicon sizes of the expected PCR products using DNA from an unaffected individual carrying no deletion of exon 3 of the RYR2 gene (left), and for DNA with the exon 3 deletion (right). The deletion size according to aCGH and the actual deletion size confirmed by Sanger-based sequencing are shown (above red lines). The expected PCR amplicon size of the deletion mutant according to the aCGH data and the actual product size are both shown. B: 2% agarose gel showing the results of PCR amplification of the genomic region encompassing exon 3 of the RYR2 gene for the proband (II-3) and her four children (III-1 to III-4). Chromatogram of the control and the proband showing where the breakpoint is (indicated by the red line).
Figure 5. Reported deletions in the RYR2 gene. Ideogram of chromosome 1 showing the location of reported RYR2 gene deletions encompassing exon 3 (shown in green, blue, and yellow bars). The location of the proband’s exon 3 deletion is shown in red, and the location and extent of Alu family repetitive sequences are shown at the bottom of the figure. These graphics were redrawn from the UCSC genome browser by accessing the NCBI36/hg18 assembly (http://genome.uscs.edu/).
Table I. Clinical summary of reported families with RYR2 exon 3 deletion. The rows shaded grey represent patients with the same deletion mutation as the current study.