Large Genomic Imbalances in Brugada Syndrome.
OBJECTIVE
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.


CONCLUSIONS
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.
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Irene
http://orcid.org/0000-0002-6501-9250
I
Mademont-Soler
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Mel Lina
ML
Pinsach-Abuin
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Helena
H
Riuró
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Jesus
J
Mates
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Alexandra
A
Pérez-Serra
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Mònica
M
Coll
Arrhythmia Unit, Hospital Universitario Donostia, San Sebastian, Spain.
José Manuel
JM
Porres
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Bernat
B
Del Olmo
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Anna
A
Iglesias
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Elisabet
E
Selga
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
Ferran
F
Picó
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.|Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.
Sara
S
Pagans
Gendiag SL, Barcelona, Spain.
Carles
C
Ferrer-Costa
Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Geòrgia
G
Sarquella-Brugada
Arrhythmia Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
Elena
E
Arbelo
Arrhythmia Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
Sergi
S
Cesar
Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.|Arrhythmia Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
Josep
J
Brugada
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.|Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.
Óscar
Ó
Campuzano
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.|Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.|Cardiovascular Genetics Unit, Hospital Josep Trueta, Girona, Spain.
Ramon
R
Brugada
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