PMC6341267_01
The 12 lead ECG in the patient. (a) The HR was 60bpm. Left axis deviation and enlarged U-waves were noted. An exercise test demonstrated polymorphic ventricular extrasystoles (b) which progressed to sustained polymorphic ventricular tachycardia (c).
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Her ECG at rest exhibited left axis deviation and QT-U prolongation (Figure 1(a)). The exercise stress testing revealed polymorphic ventricular ectopy (Figure 1(b)), which progressed to polymorphic ventricular tachycardia (Figure 1(c)) accompanied by syncope.
(a) Genetic characteristics of the proband and offspring. The result of DNA sequencing in the index patient (IV-4) demonstrating a homozygous single G to A nucleotide substation at position 1083 of the CASQ2 gene leading to a Trp361* (=W361X) stop-codon mutation. A heterozygous mutation was identified in her daughter (V-3) and son (V-4). (b) Schematic topology of CASQ2, displaying the putative location of the W361X mutation (red arrow). (c) Pedigree of the index family. The proband is marked by an arrow. The results of the CASQ2 genetic screen were performed on the index patient and her children at an age of 27 and 24, indicating a heterozygous mutation (c.1038 C/G) in the CASQ2 gene.
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This variant was validated by direct capillary sequencing (Figure 2(a)). The W361X variant resulted in the termination of the CASQ2 protein at the C-terminal region (Figure 2(b)) and was reported as pathogenic mutation for CPVT. After this homozygous mutation was identified, we further questioned the patient and discovered her parents were consanguineous (Figure 2(c)).