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Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases

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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.

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Acknowledgments

We greatly appreciate the collaboration of all persons who have kindly agreed to donate a DNA sample for this study and all institutions involved in collecting samples: CHOU from Ourense, CHUS from Santiago de Compostela, CHUVI from Vigo, Hospital Comarcal from Monforte, Hospital de la Ribera from Valencia (Dr. Ángel Zúñiga), Hospital General Universitario from Alicante, Hospital Reina Sofia from Tudela, Hospital San Pedro de Alcántara from Cáceres, Hospital Virgen de la Arrixaca from Murcia (Dr. Juan Ramón Gimeno), IMELGA and Universitary IML both from Santiago de Compostela, IML and INT from Sevilla (Dr. Joaquín Lucena), and IML from Valencia (Dra. Pilar Molina and Dr. Rafael Bañón). This work was supported by two grants from the Spanish Health Institute ISCIII (EMER07/018 and PI06/0165) to MB.

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Authors and Affiliations

  1. Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital-University Complex of Santiago (CHUS), Santiago de Compostela, Spain

    Catarina Allegue, Rocio Gil, Alejandro Blanco-Verea, Montserrat Santori & María Brion

  2. Galician Foundation of Genomic Medicine, IDIS, CIBERER-University of Santiago, Santiago de Compostela, Spain

    Catarina Allegue, Rocio Gil, Alejandro Blanco-Verea, Montserrat Santori, Ángel Carracedo & María Brion

  3. Department of Pathology and Forensic Sciences, University of Santiago de Compostela, Santiago de Compostela, Spain

    Marisol Rodríguez-Calvo & Luis Concheiro

  4. Genomics Medicine, Hospital-University Complex of Santiago (CHUS), Rua Choupana s/n, Santiago de Compostela, Spain

    María Brion

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  1. Catarina Allegue
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  2. Rocio Gil
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  7. Ángel Carracedo
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Correspondence to María Brion.

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Allegue, C., Gil, R., Blanco-Verea, A. et al. Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases. Int J Legal Med 125, 565–572 (2011). https://doi.org/10.1007/s00414-011-0572-7

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  • DOI: https://doi.org/10.1007/s00414-011-0572-7

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