Risk Stratification of Arrhythmogenic Consequences of Andersen-Tawil Syndrome Mutations Affecting Kir2.1-PIP2 Interactions
Andersen-Tawil syndrome type 1 (ATS1) is a rare but potentially lethal inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1. A total of 95 mutations have been reported to date, ~50% of which are known to impair...
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/108287 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/108287 |
| Access Level: | acceso abierto |
| Palabra clave: | 616-056.7(043.2) Enfermedades hereditarias Genética médica 2409 Genética |
| Sumario: | Andersen-Tawil syndrome type 1 (ATS1) is a rare but potentially lethal inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1. A total of 95 mutations have been reported to date, ~50% of which are known to impair the interaction of the channel with lipid cofactor phosphatidylinositol-4,5-biphosphate (also known as PI(4,5) P2 or PIP2) at the membrane. The role of PIP2 is to enable the open state of the Kir2.1 channel. A variable and heterogenous phenotype has been reported for ATS patients, however they all share common cardiac features and life-threatening manifestations, with a differential range of lethality. Therefore, the main objective of the present Doctoral Thesis was to risk stratify ATS1 patients according to the electrophysiological and molecular mechanism underlying their ventricular arrhythmias produced by KCNJ2 mutations affecting Kir2.1-PIP2 binding... |
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