Dataset Information

Whole-exome sequencing reveals two de novo variants in the RBM20 gene in two Chinese patients with left ventricular non-compaction cardiomyopathy.

ABSTRACT: Importance:Pathogenic variants in the RBM20 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 in RBM20. It remains unknown whether the variants in RBM20 associated with DCM can also cause LVNC. Objective:To elucidate the causative RBM20 variant in two unrelated patients with both LVNC and DCM, and to identify the clinical characteristics associated with variants in RBM20. 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 distinct de novo variants in RBM20 (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. A de 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 a de 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 in RBM20. Our results extended the clinical spectrum of the two RBM20 variants and illustrated that the same variant in RBM20 can cause DCM, with or without the LVNC phenotype.

SUBMITTER: Sun Q

PROVIDER: S-EPMC7331393 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Whole-exome sequencing reveals two <i>de novo</i> variants in the <i>RBM20</i> gene in two Chinese patients with left ventricular non-compaction cardiomyopathy.

Sun Qiqing Q Guo Jun J Hao Chanjuan C Guo Ruolan R Hu Xuyun X Chen Yuanying Y Yang Weili W Li Wei W Feng Yingjun Y

Pediatric investigation 20200317 1

<h4>Importance</h4>Pathogenic variants in the <i>RBM20</i> gene are associated with aggressive dilated cardiomyopathy (DCM). Recently, <i>RBM20</i> 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 in <i>RBM20</i>. It remains unknown whether the variants in <i>RBM20</i> associated with DCM can also cause LVNC.<h4>Objective</h4>To elucidate the causative <i>RBM20</i> variant in two unr ...[more]

PMID: 32851336

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Project description:Left Ventricular (LV) Non-compaction (LVNC), Hypertrophic Cardiomyopathy (HCM), and Dilated Cardiomyopathy (DCM) share morphological and functional traits that increase the diagnosis complexity. Additional clinical information, besides imaging data such as cardiovascular magnetic resonance (CMR), is usually required to reach a definitive diagnosis, including electrocardiography (ECG), family history, and genetics. Alternatively, indices of hypertrabeculation have been introduced, but they require tedious and time-consuming delineations of the trabeculae on the CMR images. In this paper, we propose a radiomics approach to automatically encode differences in the underlying shape, gray-scale and textural information in the myocardium and its trabeculae, which may enhance the capacity to differentiate between these overlapping conditions. A total of 118 subjects, including 35 patients with LVNC, 25 with HCM, 37 with DCM, as well as 21 healthy volunteers (NOR), underwent CMR imaging. A comprehensive radiomics characterization was applied to LV short-axis images to quantify shape, first-order, co-occurrence matrix, run-length matrix, and local binary patterns. Conventional CMR indices (LV volumes, mass, wall thickness, LV ejection fraction-LVEF-), as well as hypertrabeculation indices by Petersen and Jacquier, were also analyzed. State-of-the-art Machine Learning (ML) models (one-vs.-rest Support Vector Machine-SVM-, Logistic Regression-LR-, and Random Forest Classifier-RF-) were used for one-vs.-rest classification tasks. The use of radiomics models for the automated diagnosis of LVNC, HCM, and DCM resulted in excellent one-vs.-rest ROC-AUC values of 0.95 while generating these results without the need for the delineation of the trabeculae. First-order and texture features resulted to be among the most discriminative features in the obtained radiomics signatures, indicating their added value for quantifying relevant tissue patterns in cardiomyopathy differential diagnosis.

Dataset Information

Whole-exome sequencing reveals two de novo variants in the RBM20 gene in two Chinese patients with left ventricular non-compaction cardiomyopathy.

Publications

Whole-exome sequencing reveals two <i>de novo</i> variants in the <i>RBM20</i> gene in two Chinese patients with left ventricular non-compaction cardiomyopathy.

Similar Datasets

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