Large Genomic Imbalances in Brugada Syndrome

Purpose Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CN...

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Detalles Bibliográficos
Autores: Mademont Soler, Irene, Pinsach Abuin, Mel·lina, Riuró Cáceres, Helena, Matés Ramírez, Jesús, Pérez Serra, Alexandra, Coll, Mònica, Porres, José M., Olmo, Bernat del, Iglesias, Anna, Selga i Coma, Elisabet, Picó, Ferran, Pagans i Lista, Sara, Ferrer Costa, Carles, Sarquella Brugada, Georgia, Arbelo, Elena, César Diaz, Sergio, Brugada Terradellas, Josep, 1958-, Campuzano Larrea, Oscar, Brugada, Ramon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/113710
Acceso en línea:https://hdl.handle.net/2445/113710
Access Level:acceso abierto
Palabra clave:Mort sobtada
Arrítmia
Genòmica
Sudden death
Arrhythmia
Genomics
Descripción
Sumario:Purpose Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. Methods 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). Results The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. Conclusion CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes.

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