Clinical and functional characterisation of a recurrent KCNQ1 variant in the Belgian population
Summary
The c.1124_1127delTTCA frameshift variant shows a high prevalence in our region, despite not being confirmed as a founder mutation. This variant leads to a mild LQTS phenotype in the heterozygous state. Despite initial evidence for a gain-of-function effect based on in vitro electrophysiological assessment in CHO cells and expression of the KCNQ1 c.1124_1127delTTCA allele in patient blood cells, additional testing in iPSC-CMs showed lack of expression of the mutant allele. This suggests haploinsufficiency as the pathogenic mechanism. Nonetheless, as inter-individual differences in allele expression in (iPSC-) cardiomyocytes have not been assessed, a modifying effect on the BrS phenotype through potassium current modulation cannot be excluded. © 2023. The Author(s).
| Authors | Sieliwonczyk E, Alaerts M, Simons E, Snyders D, Nijak A, Vandendriessche B, Schepers D, Akdeniz D, Van Craenenbroeck E, Knaepen K, Rabaut L, Heidbuchel H, Van Laer L, Saenen J, Labro AJ, Loeys B |
|---|---|
| Journal | Orphanet journal of rare diseases |
| Publication Date | 2023 Jan 31;18(1):23 |
| PubMed | 36721196 |
| PubMed Central | PMC9887867 |
| DOI | 10.1186/s13023-023-02618-4 |