title: Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases.
abstract: Cardiomyopathies and channelopathies are major causes of sudden cardiac death. The genetic study of these diseases is difficult because of their heterogenic nature not only in their genetic traits but also in their phenotypic expression. The purpose of the present study is the analysis of a wide spectrum of previously known genetic mutations in key genes related to hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Brugada syndrome (BrS) development. The samples studied include cases of sudden cardiac death (SCD) in young adults and their relatives in order to identify the real impact of genetic screening of SCD in forensic cases. Genetic screening of described variation in 16 genes implicated in the development of HCM and three more genes implicated in LQTS and BrS was performed by using MassARRAY technology. In addition, direct sequencing of the two most prevalent genes implicated in the development of SQTL type 1 and 2 was also carried out. Genetic screening allowed us to unmask four possibly pathogenic mutation carriers in the 49 SCD cases considered; carriers of mutation represent 9% (2/23) of the probands with structural anomalies found after autopsy and 7% (1/14) of the probands with structurally normal hearts after in depth autopsy protocol. One mutation was found among 12 of the recovered SCD cases considered. In people with direct family history of sudden cardiac death, but not themselves, 11 additional mutation carriers were found. Three different mutations were found in six of the 19 LQTS patients, representing three families and two different mutations were found among six patients with previous syncope. Genetic analysis in sudden cardiac death cases could help to elucidate the cause of death, but it also can help in the prevention of future deaths in families at risk. The study presented here shows the importance and relevance of genetic screening in patients with signs of cardiac hypertrophy and in family cases with more than one relative affected.
authors.affiliation: Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital-University Complex of Santiago (CHUS), Santiago de Compostela, Spain.
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.forename: Rocio
authors.initials: R
authors.lastname: Gil
authors.forename: Alejandro
authors.initials: A
authors.lastname: Blanco-Verea
authors.forename: Montserrat
authors.initials: M
authors.lastname: Santori
authors.forename: Marisol
authors.initials: M
authors.lastname: Rodríguez-Calvo
authors.forename: Luis
authors.initials: L
authors.lastname: Concheiro
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: María
authors.initials: M
authors.lastname: Brion
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D053840:Brugada Syndrome / Q000235:genetics* / Q000473:pathology; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002423:Cause of Death; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000473:pathology* / Q000517:prevention & control; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D010641:Phenotype; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051657:KCNQ1 Potassium Channel; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human