{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:36:11Z","timestamp":1793180171801,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Andersen-Tawil Syndrome (ATS) is a rare disease defined by the association of cardiac arrhythmias, periodic paralysis and dysmorphic features, and is caused by <jats:italic>KCNJ2<\/jats:italic> loss-of-function mutations. However, when extracardiac symptoms are atypical or absent, the patient can be diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a rare arrhythmia at high risk of sudden death, mostly due to <jats:italic>RYR2<\/jats:italic> mutations. The identification of <jats:italic>KCNJ2<\/jats:italic> variants in CPVT suspicion is very rare but important because beta blockers, the cornerstone of CPVT therapy, could be less efficient. We report here the cases of two patients addressed for CPVT-like phenotypes. Genetic investigations led to the identification of p. Arg82Trp and p. Pro186Gln <jats:italic>de novo<\/jats:italic> variants in the <jats:italic>KCNJ2<\/jats:italic> gene<jats:italic>.<\/jats:italic> Functional studies showed that both variants forms of Kir2.1 monomers act as dominant negative and drastically reduced the activity of the tetrameric channel. We characterize here a new pathogenic variant (p.Pro186Gln) of <jats:italic>KCNJ2<\/jats:italic> gene and highlight the interest of accurate cardiologic evaluation and of attention to extracardiac signs to distinguish CPVT from atypical ATS, and guide therapeutic decisions. We also confirm that the <jats:italic>KCNJ2<\/jats:italic> gene must be investigated during CPVT molecular analysis.<\/jats:p>","DOI":"10.3389\/fgene.2021.773177","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:12:31Z","timestamp":1638321151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Pauline","family":"Le Tanno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Folacci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Revilloud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Pinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Amedro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Millat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Janin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vivaudou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Roux-Buisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Faur\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1093\/europace\/eur245","article-title":"HRS\/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies: This Document Was Developed as a Partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA)","volume":"13","author":"Ackerman","year":"2011","journal-title":"Europace"},{"key":"B2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1086\/342360","article-title":"KCNJ2 Mutation Results in Andersen Syndrome with Sex-specific Cardiac and Skeletal Muscle Phenotypes","volume":"71","author":"Andelfinger","year":"2002","journal-title":"Am. 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