Abstract | BACKGROUND: RESULTS: An intronic mutation (c.4810+3_4810+6dupGGGT) in the SCN5A gene, located outside the consensus splice site, was detected in this study in a family with a highly variable clinical phenotype of Brugada syndrome and/or conduction disease and in a patient with Brugada syndrome. The mutation was not found in a control panel of 100 (200 alleles) ethnically matched normal control subjects. We provide in vivo and in vitro evidence that the mutation can disrupt the splice donor site, activate a cryptic splice site, and create a novel splice site. Notably, our data show that normal transcripts can be also derived from the mutant allele. CONCLUSIONS: This is the first report of an unconventional intronic splice site mutation in the SCN5A gene leading to cardiac sodium channelopathy. We speculate that its phenotypical diversity might be determined by the ratio of normal/abnormal transcripts derived from the mutant allele.
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Authors | T Rossenbacker, E Schollen, C Kuipéri, T J L de Ravel, K Devriendt, G Matthijs, D Collen, H Heidbüchel, P Carmeliet |
Journal | Journal of medical genetics
(J Med Genet)
Vol. 42
Issue 5
Pg. e29
(May 2005)
ISSN: 1468-6244 [Electronic] England |
PMID | 15863661
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Muscle Proteins
- NAV1.5 Voltage-Gated Sodium Channel
- RNA Splice Sites
- SCN5A protein, human
- Sodium Channels
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Topics |
- Adolescent
- Adult
- Aged
- Alleles
- Arrhythmias, Cardiac
(genetics)
- Child
- DNA Mutational Analysis
- Female
- Humans
- Introns
(genetics)
- Male
- Middle Aged
- Models, Biological
- Muscle Proteins
(genetics)
- Mutation
- NAV1.5 Voltage-Gated Sodium Channel
- Pedigree
- RNA Splice Sites
(genetics)
- RNA Splicing
(physiology)
- Sodium Channels
(genetics)
- Syndrome
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