“Genetic Analysis of Inherited Cardiac diseases in Cypriot patients”
Date
2022-12-22Author
Vangeli, DespoinaPublisher
Πανεπιστήμιο Κύπρου, Ιατρική Σχολή / University of Cyprus, Medical SchoolGoogle Scholar check
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Introduction: Cardiomyopathies are defined as disorders of the cardiac muscle and
considered as the leading cause of sudden death in young athletes worldwide. The
following study emphasizes on inherited cardiac diseases which are classified into
cardiomyopathies and channelopathies, and there are several sub-categories based on
the clinical and genetic phenotype. Inherited cardiomyopathies are divided into 4 subgroups: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM),
arrhythmogenic right ventricular cardiomyopathy (ARVC) and restrictive
cardiomyopathy (RCM). The most common inherited channelopathies are divided
into long QT syndrome (LQTS), short QT syndrome (SQTS), catecholaminergic
polymorphic ventricular tachycardia (CPVT) and Brugada syndrome.
Objective: The main objective of the project was the genetic analysis of the DNA of
probands with a suspicion of an inherited form of a cardiac disease, to identify genetic
alterations that could be related to the probands’ clinical phenotype and identify the family
members at risk.
Methods: The genetic variations in probands’ DNA samples were identified through Next
Generation Sequencing (NGS) using a panel of 72 genes related to cardiac diseases. The NGS
results were validated through Sanger Sequencing. Once the proband was validated positive
for a genetic variation, the testing was repeated for every family member with an available
DNA sample. Once the validation of the results was completed, the pathogenicity of the
genetic variants under study was evaluated in different databases (HGMD, ClinVar, Franklin,
Varsome). Furthermore, bioinformatic algorithms were used to predict the pathogenicity at
the cDNA level and protein level (Mutation taster, Polyphen-2, SIFT).
Results: In this study, 11 families were examined with the panel of the 72 genes, and 25
genetic variations were identified, 20 of them novel. Most of the variants are responsible for
probands clinicals phenotype although patterns of incomplete penetrance and co-inheritance
of multiple genetic variants have been observed.
Conclusions: Inherited cardiac diseases are characterized by genetic and phenotypic
heterogeneity. The results indicate that in some cases these disorders may have oligogenic
inheritance pattern, however further studies are required to verify it. Finally, To our
knowledge, this is the first systematic study attempted in Cyprus for inherited cardiac
conditions, enabling us to develop information about the genetic basis of these diseases and
guidelines for new therapeutic approaches.