Projects per year
We performed SCN5A mutation analysis of all 27 translated exons and flanking intron-exon boundaries 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. In total phenotypic data (baseline and ajmaline-induced ECG) of 44 patients were compared with genotypic data (SCN5A mutation analysis). 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.
|Title of host publication||Abstract book of the 13th Annual Meeting of the Belgian Society of Human Genetics|
|Number of pages||1|
|Publication status||Published - 15 Mar 2013|
|Event||13th Annual meeting of the Belgian Society of Human Genetics - EXPO, Brussels, Belgium|
Duration: 15 Mar 2013 → 15 Mar 2013
|Conference||13th Annual meeting of the Belgian Society of Human Genetics|
|Period||15/03/13 → 15/03/13|
- Brugada syndrome
ADSI311: Interne overdracht voor aanstelling van doctoraat Dorien DANEELS Unraveling the molecular genetic pathway of Brugada syndrome
1/03/12 → 31/12/12