Abstract
BackgroundCardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. Although different mechanisms underlie the various types of cardiomyopathies, a principal pathology is common to all and is usually at the level of the cardiac muscle. With a relatively high incidence rate in most countries, and a subsequent major health burden on both the families and governments, cardiomyopathies are gaining more attention by researchers and pharmaceutical companies as well as health government bodies. In Lebanon, there is no official data about the spectrum of the diseases in terms of their respective prevalence, clinical, or genetic profiles.MethodsWe used exome sequencing to unravel the genetic basis of idiopathic cases of cardiomyopathies in Lebanon, a relatively small country with high rates of consanguineous marriages.ResultsFive cases were diagnosed with different forms of cardiomyopathies, and exome sequencing revealed the presence of already documented or novel mutations in known genes in three cases: LMNA for an Emery Dreifuss Muscular Dystrophy case, PKP2 for an arrhythmogenic right ventricle dysplasia case, and MYPN for a dilated cardiomyopathy case. Interestingly two brothers with hypertrophic cardiomyopathy have a novel missense variation in NPR1, the gene encoding the natriuretic peptides receptor type I, not reported previously to be causing cardiomyopathies.ConclusionOur results unravel novel mutations in known genes implicated in cardiomyopathies in Lebanon. Changes in clinical management however, require genetic profiling of a larger cohort of patients.
Highlights
Cardiomyopathies affect more than 0.5% of the general population
The pathogenic variant in the Lamin A/C gene LMNA was previously reported as de novo mutation arising in a family from the United Kingdom (UK)
The data summarized in Additional file 1: Table S4, showed 73 missense variants with some genes being directly or indirectly deregulated in hypertrophy like Fibulin2, and Fibrillin 3. This is the first study in Lebanon and in the region where whole exome sequencing technology has been implemented on patients with primary cardiomyopathy without a previous family history of the disease
Summary
Cardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. More than 1000 mutations have been linked to the 5 different classes of cardiomyopathies in more than 40 genes mainly encoding contractile proteins regulating the contraction of the cardiomyocytes [1]. Population based genetic testing and in vitro assessment of defective proteins, have helped tremendously in understanding the molecular basis of the different phenotypes yet, there are many challenges towards implementing common therapeutical and interventional guidelines. The importance of genetic testing and research in cardiomyopathy for its implications on diagnosis, prognostication, and counseling
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