Answer to Question #294262 in English for Collen

Question

Mutation Analysis of the Candidate Genes SCNIB-4B, FHL1, and LMNA in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart disease characterized by fibrofatty infiltrations in the myocardium, right and/or left ventricular involvement, and ventricular tachyarrhythmias. Although ten genes have been associated with ARVC, only about 40% of the patients have an identifiable disease causing mutation. In the present study we aimed at investigating the involvement of the genes SCNIB-SCN4B, FHL1, and LMNA in the pathogenesis of ARVC.

RESULTS: A total of 28 sequence variants were identified: seven in SCN1B, three in SCN2B, two in SCN3B, two in SCN4B, four in FHL1, and ten in LMNA. Three of the variants were novel. One of the variants was non-synonymous. No disease-causing mutations were identified.

ANSWER THE FOLLOWING:

A. IMPORTANT TERMINOLOGIES USED IN THE TEXT: 

Answer 1

ARVC (arrhythmogenic right ventricular cardiomyopathy) is a genetically determined cardiac disease marked by myocardial fibrofatty infiltrations, right and/or left ventricular involvement, and ventricular tachyarrhythmias. Despite the fact that ten genes have been linked to ARVC, only about 40% of patients have a disease-causing mutation. If molecular genetic results are used as part of the diagnostic scoring system, the current understanding of the genetic basis of ARVC is limited, and there is a lot of genetic noise due to common disease-associated genetic variants in both the normal population and other cardiomyopathies, which increases the risk of misdiagnosis.Genotyping is indicated to identify a pathogenic or likely pathogenic mutation in a proband who already meets phenotypic diagnostic criteria for ARVC, and thus to apply mutation-specific cascade genetic testing for detection of gene carriers among family members, according to general recommendations for molecular genetic testing in inherited cardiomyopathies. Following the discovery of a pathogenic or suspected pathogenic mutation in the proband with a clinical diagnosis of confirmed ARVC, mutation-specific genetic testing is recommended for family members in order to detect genetically affected persons at a preclinical stage.