Natural History of Dilated Cardiomyopathy Due to c.77T>C (p.Val26Ala) in Emerin Protein.

(1)

Introduction

Dilated cardiomyopathy (DCM) mainly affects young individuals and is the main indication of heart transplantation. The variant c.77T>C (p.Val26Ala) of the gene coding for emerin (EMD) in chromosome Xq28 has been catalogued as a pathogenic variant for the development of DCM, exhibiting an X-linked inheritance pattern. (2)

Methods

A retrospective study was conducted covering the period 2015-2023 in patients with DCM of genetic origin. The primary endpoint was patient age at onset of the first composite major cardiac event, in the form of a first episode of heart failure, malignant ventricular arrhythmia, or end-stage heart failure, according to the presence of truncating variant in titin gene (TTNtv) versus the p.Val26Ala mutation in the EMD protein. (3)

Results

A total of 31 and 22 patients were included in the EMD group and TTNtv group, respectively. The primary endpoint was significantly higher in the EMD group, with a hazard ratio of 4.16 (95% confidence interval: 1.83-9.46; p = 0.001). At 55 years of age, all the patients in the EMD group had already presented heart failure, nine presented malignant ventricular arrhythmia (29%), and 13 required heart transplantation (42%). (4)

Conclusions

DCM secondary to the c.77T>C (p.Val26Ala) mutation in the EMD gene is associated to an increased risk of major cardiac events compared to patients with DCM due to TTNtv, with a large proportion of transplanted patients in the fifth decade of life.