Pathogenic variant of RBM20 in a multiplex family with hypertrophic cardiomyopathy

Figures

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  Fig. 1. Clinical profile of a family with HCM. A Family pedigree showing the inheritance of cardiomyopathy. Squares denote males and circles denote females. Black symbols indicate affected individuals and open symbols indicate unaffected individuals. Gray symbols indicate individuals showing left ventricular hypertrophy on an electrocardiogram. The arrow indicates patients diagnosed with cardiomyopathy. P proband, d death, E genetic evaluation, + presence of RBM20 variant, − absence of RBM20 variant. B Short-axis images of cardiac magnetic resonance (CMR) for the proband (III-3) and her mother (II-2). The top and middle rows present end-diastolic and end-systolic cine images, respectively, and the bottom row shows extracellular volume (ECV) fraction mapping. Both III-3 and II-2 demonstrated elevated ECV (light green colored, arrowheads), primarily in the ventricular septum. RV right ventricle, LV left ventricle.

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  Fig. 2. Identification of a pathogenic variant of RBM20. A Sanger sequencing results of the RBM20 (NM_001134363.3) gene in healthy controls (left panel) and patients (right panel) are shown. The patients carry a heterozygous missense variant, NM_001134363.3 (RBM20_v001): c.1907 G > A, p.Arg636His. B In the RS region (marked in black) located in codons 613 to 673 of RBM20, all variants (upper row) of RBM20 that were registered as “pathogenic” or “likely pathogenic” in the ClinVar database are located in the RSRSP stretch domain (codons 634 to 638), shown in red. These variants were all found in patients with DCM. The variant (RBM20 p.R636H) found in this family with HCM (bottom row) is also located in the RSRSP stretch domain. DCM dilated cardiomyopathy, HCM hypertrophic cardiomyopathy.