A combinatorial oligogenic basis for the phenotypic plasticity between late-onset dilated and arrhythmogenic cardiomyopathy in a single family

Figures

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  Figure 1.. Pedigree and list of the likely pathogenic variants (LPVs) in genes known to cause cardiomyopathies. Generation and family member identifiers are listed, the latter under each symbol. Gene name and the amino acid change or splice variants are listed under each symbol, indicating presence of the variants in that exome. Square: male; Circle: female; Full circle and square: affected individuals; Open circle and square: unaffected individuals; slash through: deceased individuals. Circle and square with a dot at the center indicate carrier individuals or obligate carrier (II-1). Gray circle with white center identifies an individual with ARVC.

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  Figure 2.. A 12-lead electrocardiogram in the proband (the upper three panels) and a rhythm strip (lower three panels). The electrocardiogram shows a normal sinus rhythm, probable left atrial enlargement, a normal PR interval, and an increased QRS duration with a normal axis and morphology, indicative of left bundle branch block.

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  Figure 3.. Echocardiogram and cardiac magnetic image resonance in the proband. Panels A and B show parasternal long axis view of the ventricles in diastole (panel A) and systole (Panel B). The left ventricular end diastolic and systolic diameters were measured 5.64 and 4.47 cm, respectively, and a calculated left ventricular fractional shortening of 21%. Panel C shows myocardial tissue Doppler velocities depicting low velocities. Panel D shows cross sectional myocardial images obtained by magnetic resonance imaging, which shows enlarged ventricles and absence of fibrofatty infiltration of the myocardium.

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  Figure 4.. Histological findings in a family member with the classic ARVC. Masson trichrome stained myocardial sections, low (upper panel) and high magnification (lower panel) fields, from the right and left ventricles of family member III-4 who died suddenly. Sections from the right ventricle showing infiltration of the right ventricular wall with fibro-adipocytes, whereas the section from the left ventricle shows mild fibrosis.