PMC5412645_01
A: A 2-dimensional echocardiogram recorded on admission. Bidirectional arrows indicate a noncompaction layer, and solid lines indicate a compaction layer in the left ventricle. Note the prominent trabeculations and deep intertrabecular recesses in the left ventricle. B: Lead II monitor electrocardiogram recorded on hospital day 14 showing sustained ventricular tachycardia with a heart rate of 150-170 bpm. C: The images shows the epicardial bipolar electrodes placed on the right atrium and ventricle, the shock coil placed on posterior of the left atrium through transverse sinus, and the implantable cardioverter defibrillator placed in the intraperitoneal space.
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A 2-dimensional echocardiogram revealed prominent trabeculations and deep intertrabecular recesses at the apical, anterolateral, and posterior regions of the left ventricle (Figure 1A). On hospital day 14, recurrent attacks of ventricular tachycardia at 170 beats per minute were observed on ECG monitoring (Figure 1B); the patient was treated with intravenous landiolol (an ultrashort-acting beta1-blocker) in addition to the oral amiodarone. A secondary prevention epicardial implantable cardioverter defibrillator was placed (Figure 1C).
A: Sequence analysis of exon 5 in ACTC1 of the proband showing results for the DNA sample isolated from a blood sample. The electropherograms show the heterozygous C>G substitution resulting in the threonine-to-arginine missense mutation. The putative amino acid sequence is shown above the nucleotide sequence. B: Alignment of the regions flanking the novel mutation in ACTC1 showing evolutionary conservation of the mutated residue across species (boxed). Dots indicate amino acids identical to the one in the human sequence. C: Structure of the ACTC1 indicating the position of the mutations previously described (black) and our novel variant (red), which are all highly conserved across species. ASD = atrial septal defect; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; LVNC = left ventricular noncompaction; RCM = restrictive cardiomyopathy.
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A novel heterozygous missense variant in ACTC1 (c.692C>G, p.T231R) was identified (Figure 2A), and it was considered to be possibly pathogenic on in silico analysis. Information's dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/) or the National Heart, Lung, and Blood Institute's Grand Opportunity Exome Sequencing Project Exome Variant Server (http://evs.gs.washington.edu/EVS/); (4) it affected evolutionarily conserved residues (nucleotide and amino acid: Figure 2B); and (5) it was predicted to be deleterious/pathogenic by multiple in silico algorithms (Polyphen2, PANTHER, Align GVGD, SIFT, and Mutation Taster). No mutation was identified in the TAZ, LMNA/C, LDB3, DTNA, MIB1, PRDM16, YWHAE, MYBPC3, TNNT2, TNNI3, ACTC, or TPM1 gene. In addition, no mutation was identified in RYR2 or CASQ2, where several mutations have been identified in patients with catecholaminergic polymorphic ventricular tachycardia.