| Autor: |
Van Dooren, Sonia, Brugada, Pedro, Daneels, Dorien, Peeters, Uschi, Peirsman, Liszl, Timmermans, Inge, Kindermans, Kiliana, Biervliet, Martine, Pappaert, Gudrun, Bonduelle, Mary-Louise |
| Přispěvatelé: |
Department of Embryology and Genetics, Reproduction and Genetics, Cardio-vascular diseases |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Popis: |
Brugada syndrome is one of common inheritable arrhythmogenic disorders in apparently structurally normal hearts, inherited as an autosomal dominant trait with incomplete penetrance and variable expression. Clinical diagnosis is based on documented ventricular arrhythmias and/or related symptoms, family history AND a type 1 spontaneous or sodium-blocker induced ST-segment ECG elevation. Genetic diagnosis is currently still based on the mutation analysis of the pore-forming alfa-subunit of the sodium channel gene(SCN5A), resulting in a genetic diagnostic yield of approximately 20%. We performed SCN5A mutation analysis in 135 Brugada syndrome probands of our outclinic patient population. We identified 20 variants of which 17 described mutations and 3 novel potential disease causing variants by in silico prediction tools, resulting in a diagnostic yield of respectively 12,6% to 14,8% (3 variants included). Subsequent segregation analysis was performed in 8 large families of the identified SCN5A positive BrS probands to determine genotype-phenotype correlation. A sensitivity of 76% and specificity of 79% was assessed and could be increased up to 85% and 92% respectively with exclusion of the undescribed SCN5A variants. Revision of all ECG data revealed that some ajmaline or baseline ECG negative BrS patients with SCN5A mutations did not meet the stringent diagnostic criteria but demonstrated conduction disease. These results urge for the need to revise the clinical diagnostic criteria for Brugada syndrome, especially since the ajmaline ECG data are of important added value for this low penetrant disorder in the discovery of novel major molecular genetic pathways in Brugada syndrome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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