A Pathogenic Nonsense Mutation (c.1522C>T) of the MYBPC3 Gene is Implicated with Hypertrophic Cardiomyopathy

Figures

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  Figure 1. The index patient's initial 12‐lead ECG on admission. ECG showed a totally irregular RR interval, widened QRS complexes, and fibrillary waves instead of visible P waves. QS pattern existed in II‐aVF and V4–V6 leads. R‐wave progression was poor in the V1–V3 leads. The ST‐segment elevation was presented in the inferior leads. Reciprocal ST‐segment depression and T wave inversion occurred in the I and aVL leads.

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  Figure 2. Clinical imaging findings of the index patient on admission. (A) In 2D echocardiography, the parasternal long‐axis (PLA) view (left) showed LV enlargement and hypertrophy. In colour Doppler echocardiography, the apical 4‐chamber view (right) showed mild mitral valve regurgitation. (B) Exercise stress echocardiography test. At rest (left), the patient showed a peak LVOT velocity of 87 cm/s and a gradient of 3 mmHg; post‐exercise (right), the patient showed a peak LVOT velocity of 118 cm/s and a gradient of 6 mmHg. The heart rate reserve (HRR) was normal (rest = 64 b.p.m.; peak exercise = 121 b.p.m.; HRR = 1.89). (C) Representative CMR 4‐chamber cine image showed the enlargement of left heart (inner diameter: left atrium, 59.2 mm; left ventricle, 61.6 mm) and asymmetric left ventricular hypertrophy, especially in the middle segment of the interventricular septum (20 mm). (D) Representative CMR‐LGE image showed myocardial fibrosis with significant high signal intensity. (E) Example of computerized tomography coronary angiography 3D reconstruction. D1, first diagonal branch; D2, second diagonal branch; LAD, left anterior descending; LCX, left circumflex; OM1, first obtuse marginal…

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  Figure 3. Pedigree and genetic analysis of the index's family. (A) Family members who are affected by HCM and SCD are indicated with black and red shading, respectively. Family members with unknown healthy conditions are indicated with a question mark. Deceased family members are indicated with diagonal line. The male index patient (II‐9) with the MYBPC3 variant (*) is indicated with an arrow. IV‐4 carries both MYBPC3 (*) and ACTC1 variants (#). (B) Sanger sequencing (reverse strands) analysis confirmed the presence of the heterozygous nonsense MYBPC3 c.1522C>T variant (red arrows) in the index patient (II‐9) and IV‐4.