Exclusion of multiple candidate genes and large genomic rearrangements in SMA in a Dutch Brugada syndrome cohort

被引:38
作者
Koopmann, Tamara T.
Beekman, Leander
Alders, Marielle
Meregalli, Paola G.
Mannens, MarceL M. A. M.
Moorman, Antoon F. M.
Wide, Arthur A. M.
Bezzina, Connie R.
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Expt Cardiol, Ctr Heart Failure Res,Expt & Mol Cardiol Grp, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
关键词
Brugada syndrome; genetics; mutation; polymorphism; sodium channels; Iroquois homeobox transcription factors; adherens junctions; caveolin-3; GPD1L;
D O I
10.1016/j.hrthm.2007.02.021
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND The Brugada syndrome is an inherited cardiac electrical disorder associated with a high incidence of life-threatening arrhythmias. Screening for mutations in the cardiac Na+ channel-encoding gene SCN5A uncovers a mutation in approximately 20% of Brugada syndrome cases. Genetic heterogeneity and/or undetected SCN5A mutations, such as exon duplications and deletions, could be involved in the remaining 80% mutation-negative patients. OBJECTIVES Thirty-eight SCN5A mutation-negative Dutch Brugada syndrome probands were studied. The SCN5A gene was investigated for exon duplication and deletion, and a number of candidate genes (Caveolin-3, Irx-3, Irx-4, Irx-5, Irx-6, Plakoglobin, Plakophilin-2, SCN1B, SCN2B, SCN3B, and SCN4B) were tested for the occurrence of point mutations and small insertions/deletions. METHODS We used a quantitative multiplex approach to determine SCN5A exon copy numbers. Mutation analysis of the candidate genes was performed by direct sequencing of polymerase chain reaction-amplified coding regions. RESULTS No large genomic rearrangements in SCN5A were identified. No mutations were found in the candidate genes. Twenty novel polymorphisms were identified in these genes. CONCLUSION Large genomic rearrangements in SCN5A are not a common cause of Brugada syndrome. Similarly, the studied candidate genes are unlikely to be major causal genes of Brugada syndrome. Further studies are required to identify other genes responsible for this syndrome.
引用
收藏
页码:752 / 755
页数:4
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