2026-06-14T03:44:14Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/154262024-09-27T09:35:43Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Manuel, Ana Isabel Moreno author Gutiérrez, Lilian K author Pedrosa, María Linarejos Vera author Uréndez, Francisco Miguel Cruz author Jiménez, Francisco José Bermúdez author Carrascoso, Isabel Martínez author Pérez, Patricia Sánchez author Macías, Álvaro author Jalife, Jose author 2022-07-27 Andersen Tawil Syndrome (ATS) is a rare inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1, which forms an essential membrane protein controlling cardiac excitability. ATS is usually marked by a triad of periodic paralysis, life-threatening cardiac arrhythmias and dysmorphic features, but its expression is variable and not all patients with a phenotype linked to ATS have a known genetic alteration. The mechanisms underlying this arrhythmogenic syndrome are poorly understood. Knowing such mechanisms would be essential to distinguish ATS from other channelopathies with overlapping phenotypes and to develop individualized therapies. For example, the recently suggested role of Kir2.1 as a countercurrent to sarcoplasmic calcium reuptake might explain the arrhythmogenic mechanisms of ATS and its overlap with catecholaminergic polymorphic ventricular tachycardia (CPVT). Here we summarize current knowledge on the mechanisms of arrhythmias leading to sudden cardiac death in ATS. We first provide an overview of the syndrome and its pathophysiology, from the patient´s bedside to the protein, and discuss the role of essential regulators and interactors that could play a role in cases of ATS. The review highlights novel ideas related to some post-translational channel interactions with partner proteins that might help define the molecular bases of the arrhythmia phenotype. We then propose a new all-embracing classification of the currently known ATS loss-of-function mutations according to their position in the Kir2.1 channel structure and their functional implications. We also discuss specific ATS pathogenic variants, their clinical manifestations and treatment stratification. The goal is to provide a deeper mechanistic understanding of the syndrome toward the development of novel targets and personalized treatment strategies. Cardiovasc Res. 2022 Jul 27; cvac118 10.1093/cvr/cvac118 1755-3245 Cardiovascular research 35892314 http://hdl.handle.net/20.500.12105/15426 Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil Syndrome.