RBM20 nucleotide sequence variant in a family with a dilated phenotype of left ventricular non-compaction

Aim. To demonstrate two generations of a family with a progressive course of left ventricular non-compaction (LVNC) and the presence of a RBM20 gene variant.

Material and methods. Based on the multicenter registry of patients with LVNC, a family with LVNC with a dilated phenotype was selected at the National Medical Research Center for Therapy and Preventive Medicine. Next generation sequencing was performed on a Nextseq 550 systen (Illumina, USA). For clinical interpretation, nucleotide sequence variants in the genes associated with LVNC development were selected according to the available literature data, with frequencies <0,5% in the gnomAD database. The identified variants were verified using Sanger sequencing on an Applied Biosystem 3500 Genetic Analyzer (Thermo Fisher Scientific, USA).

Results. The article presents the results of clinical, paraclinical and molecular genetic studies of two generations of a family diagnosed with LVNC with a dilated phenotype and the progression of isolated LVNC to a dilated type. As a result of a molecular genetic study, all family members with the LVNC were found to have a likely pathogenic variant in the RBM20 NP_001127835.2:p.Pro638Leu (rs267607003) gene. RBM20 is a key splicing regulator that controls the processing of several important transcripts predominantly expressed in striated muscle, especially cardiac tissue. RBM20 gene variants can lead to disruption of splicing at several points and, as a result, to cardiomyopathy progression. Most known pathogenic RBM20 variants are associated with dilated cardiomyopathy; however, a number of studies have found RBM20 gene variants in patients with LVNC. The segregation of nucleotide sequence variant with symptoms in two generations testifies in favor of the association of the detected variant with LVNC development.

Conclusion. Currently, the boundaries of the cardiomyopathy genetics are expanding. Pathogenic and likely pathogenic RBM20 gene variants are associated primarily with a dilated phenotype and a high risk of sudden cardiac death. The article presents the results of a survey of two generations of a family with LVNC and progressive myocardial remodeling.

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