Key result
Large genomic imbalances in SCN5A are uncommon among genotype-negative Brugada syndrome patients, with a detection rate of 0.45% (1/220).
Why the study?
Does screening for copy number variants (CNVs) in SCN5A and minor genes improve genetic diagnosis in genotype-negative Brugada syndrome patients?
Observational (n=220)
Yes
Does screening for copy number variants (CNVs) in SCN5A and minor genes improve genetic diagnosis in genotype-negative Brugada syndrome patients?
Copy number variants in SCN5A and minor genes are rare in genotype-negative Brugada syndrome patients, suggesting they do not have a major contribution to the disease.
CNV screening adds little diagnostic yield in genotype-negative Brugada syndrome; leaves open broader genomic contributions.
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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Mademont‐Soler et al. (2016) conducted an observational in Brugada Syndrome (n=220). Genetic screening for Copy Number Variants (CNVs) was evaluated on Detection rate of CNVs in SCN5A. Large genomic imbalances in SCN5A are uncommon among genotype-negative Brugada syndrome patients, with a detection rate of 0.45% (1/220).
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