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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 (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

Public Library of Science (PLoS)

Autor: Mademont Soler, Irene
Pinsach Abuin, Mel·lina
Riuró Cáceres, Helena
Matés Ramírez, Jesús
Pérez Serra, Alexandra
Coll, Monica
Porres, José M.
Olmo, Bernat del
Iglesias, Anna
Selga Coma, Elisabet
Picó, Ferran
Pagans i Lista, Sara
Ferrer Costa, Carles
Sarquella Brugada, Georgia
Arbelo, Elena
Cesar, Sergi
Brugada Terradellas, Josep
Campuzano Larrea, Oscar
Brugada, Ramon
Resum: 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
Accés al document: http://hdl.handle.net/2072/298564
Llenguatge: eng
Editor: Public Library of Science (PLoS)
Drets: Reconeixement 3.0 Espanya
URI Drets: http://creativecommons.org/licenses/by/3.0/es
Matèria: Mort sobtada
Sudden death
Arítmia
Arrhythmia
Títol: Large Genomic Imbalances in Brugada Syndrome
Tipus: info:eu-repo/semantics/article
Repositori: Recercat

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