CASE SERIES OF DILATED CARDIOMYOPATHY STUDIED WITH WHOLE GENOME SEQUENCING

Abstract

Objective: The explanation of the genetic aspects of dilatative cardiomyopathy (DCM) is important for at least two major reasons: 1. there is a phenotypic and clinical overlap between the various cardiomyopathies with DCM - thus it might be suggested DCM may be an end phenotype; 2. genetic predisposition to DCM might render the myocardium susceptible to various exogenous factors such as infections, alcohol, toxins, etc. Design and method: We share the results from the Next Gene sequencing of 10 patients with DCM. They were of various ages, with the inclusion requirement to be without coronary or hypertensive disease, and clinical manifestations of the DCM from yearly age. Bioinformatics analysis of the data was done with the appropriate protocol on a Dragen server, as well as VarSeq (Goldenhelix) for all NGS data. Results: This case series of Caucasian patients with DCM presented with mutations in TTN, TTN-AS1, SCN5A, RYR2, DSG2, DSG2-AS1, FLNC, LAMA4, ACTN2, GATA6, DMD genes. All these genes are responsible for structural sarcomere, nucleus proteins or ion transporters. They are common also in arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, muscular dystrophy and Brugada syndrome. Omim search found them as VUS or weak pathogenic and only a mutation in TTN as likely pathogenic. Nevertheless, the cumulation of data for the genetic aspects of cardiomyopathies is important. The echocardiographic ejection fraction of the patients varied with the medical treatment and could not be used as guiding in their risk assessment. Conclusions: As far as the ejection fraction and left ventricular morphology are modifiable factors, we need a more specific way to assess the inherent risk in our cardiac patients. NGS might provide the necessary information, but we need to accumulate clinical and genetic data to make specific cardiomyopathy risk profiles. These risk profiles should be based on genetic analysis and not on ejection fraction or other morphological criteria, as we have cardiomyopathies’ overlap.