Novel compound heterozygous ALPK3 mutations (c.4234C>T and c.3491G>A), causing hypertrophic cardiomyopathy treated with the liwen procedure: case report

Figures

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  Figure 1. (A) Extracardiac manifestations in patients with compound heterozygous mutations in the ALPK3 gene: palms with simian creases in both hands. (B) Electrocardiogram. The electrocardiogram showed left ventricular hypervoltage and myocardial ischemia. (C) Preoperative cardiac magnetic resonance: Four-chamber view of the heart; Short-axis views of the left ventricle (end diastole). Diffuse hypertrophy of the left ventricle and thickening of the RVFW were observed. End-diastolic measurements revealed an IVS thickness of 29 mm and an RVFW thickness of 8 mm. Late gadolinium enhancement was absent in the septum and the mid-to-distal segments of the left ventricle.

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  Figure 2. (A) family tree of ALPK3 gene mutation. □ Male, ○ Female, ● Patient, Carrier, Proband. (B) Sanger sequencing of the proband's first-degree relatives.(C) Variant frequency analysis of the ALPK3 mutations (c.4234C > T nonsense and c.3491G > A missense) across three major population genomic databases (gnomAD, ExAC, 1,000 Genomes Project) demonstrated.(D) The domain architecture and mutation distribution of ALPK3:Distribution of pathogenic variants in ALPK3 across populations in China and abroad. Red indicates carriers in the Chinese population, while black indicates carriers in non-Chinese populations.(E) Pathogenic variants in the ALPK3 gene exhibit specific distribution characteristics within human populations. Pathogenic mutations in this gene primarily occur in exons 5, 6, and 10. Variations in these three exons account for 72.52% of all reported cases. Variations in exon 4 (60%) and exon 10 (40%) are more prevalent in the Chinese population than the global average, suggesting potential racial specificity.

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  Figure 3. Transthoracic echocardiography. (A) Preoperative transthoracic echocardiography demonstrates severe left ventricular hypertrophy, right ventricular free wall hypertrophy, and a small LVEDV in parasternal long axis of left ventricule, parasternal short axis, and apical four-chamber view. (B) A 6-month postoperative transthoracic echocardiography, compared with (A), reveals significant thinning of both the left ventricular and right ventricular free wall myocardium, alongside a marked increase in LVEDV.