Importance:Pathogenic variants in theRBM20 gene are associated with aggressive dilated cardiomyopathy(DCM).Recently,RBM20 was found to be associated with left ventricular non-compaction cardiomyopathy(LVNC).Thus far,o...Importance:Pathogenic variants in theRBM20 gene are associated with aggressive dilated cardiomyopathy(DCM).Recently,RBM20 was found to be associated with left ventricular non-compaction cardiomyopathy(LVNC).Thus far,only five families with LVNC have been reported to carry variants inRBM20.It remains unknown whether the variants inRBM20 associated with DCM can also cause LVNC.Objective:To elucidate the causativeRBM20 variant in two unrelated patients with both LVNC and DCM,and to identify the clinical characteristics associated with variants inRBM20.Methods:Trio whole-exome sequencing(WES)was performed.Variants were filtered and classified in accordance with the guidelines of the American College of Medical Genetics and Genomics(ACMG).Results:We identified two distinctde novo variants inRBM20(one per patient)in these two patients with LVNC.Both variants have been reported in patients with DCM,without the LVNC phenotype.Patient 1 was an 11-year-old girl who had DCM,LVNC,and heart failure;the ratio of noncompacted-to-compacted myocardium was 2.7:1.Ade novo heterozygous variant c.1907G>A(p.Arg636His)in exon 9 was identified in this patient.Patient 2 was a 13-year-old boy who had clinical phenotypes identical to those of Patient 1;the ratio of noncompacted-to-compacted myocardium was 3.2:1 in this patient.WES revealed ade novo heterozygous variant c.1909A>G(p.Ser637Gly)in exon 9.Both variants were previously characterized as pathogenic,and our study classified them as pathogenic variants based on the ACMG guidelines.Interpretation:We found that two patients with LVNC had variants inRBM20.Our results extended the clinical spectrum of the twoRBM20 variants and illustrated that the same variant inRBM20 can cause DCM,with or without the LVNC phenotype.展开更多
文摘Importance:Pathogenic variants in theRBM20 gene are associated with aggressive dilated cardiomyopathy(DCM).Recently,RBM20 was found to be associated with left ventricular non-compaction cardiomyopathy(LVNC).Thus far,only five families with LVNC have been reported to carry variants inRBM20.It remains unknown whether the variants inRBM20 associated with DCM can also cause LVNC.Objective:To elucidate the causativeRBM20 variant in two unrelated patients with both LVNC and DCM,and to identify the clinical characteristics associated with variants inRBM20.Methods:Trio whole-exome sequencing(WES)was performed.Variants were filtered and classified in accordance with the guidelines of the American College of Medical Genetics and Genomics(ACMG).Results:We identified two distinctde novo variants inRBM20(one per patient)in these two patients with LVNC.Both variants have been reported in patients with DCM,without the LVNC phenotype.Patient 1 was an 11-year-old girl who had DCM,LVNC,and heart failure;the ratio of noncompacted-to-compacted myocardium was 2.7:1.Ade novo heterozygous variant c.1907G>A(p.Arg636His)in exon 9 was identified in this patient.Patient 2 was a 13-year-old boy who had clinical phenotypes identical to those of Patient 1;the ratio of noncompacted-to-compacted myocardium was 3.2:1 in this patient.WES revealed ade novo heterozygous variant c.1909A>G(p.Ser637Gly)in exon 9.Both variants were previously characterized as pathogenic,and our study classified them as pathogenic variants based on the ACMG guidelines.Interpretation:We found that two patients with LVNC had variants inRBM20.Our results extended the clinical spectrum of the twoRBM20 variants and illustrated that the same variant inRBM20 can cause DCM,with or without the LVNC phenotype.
