{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:12:35Z","timestamp":1781143955448,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["20-54-15004"],"award-info":[{"award-number":["20-54-15004"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The KCNJ2 gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and\/or atrial fibrillation. Methods: We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells. Results: We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III). Conclusions: LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated.<\/jats:p>","DOI":"10.3390\/genes13040559","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Variable Clinical Appearance of the Kir2.1 Rare Variants in Russian Patients with Long QT Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Elena","family":"Zaklyazminskaya","sequence":"first","affiliation":[{"name":"Medical Genetics Laboratory, B.V. Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-1945","authenticated-orcid":false,"given":"Margarita","family":"Polyak","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, B.V. Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4596-8950","authenticated-orcid":false,"given":"Anna","family":"Shestak","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, B.V. Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Sadekova","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, B.V. Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3691-7449","authenticated-orcid":false,"given":"Vera","family":"Komoliatova","sequence":"additional","affiliation":[{"name":"Center for Syncope and Cardiac Arrhythmias in Children and Adolescents, Federal Medical Biological Agency, 115481 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"Center for Syncope and Cardiac Arrhythmias in Children and Adolescents, Federal Medical Biological Agency, 115481 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Makarov","sequence":"additional","affiliation":[{"name":"Center for Syncope and Cardiac Arrhythmias in Children and Adolescents, Federal Medical Biological Agency, 115481 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Podolyak","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, B.V. Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigory","family":"Glukhov","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen 517182, China"},{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen 517182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Abramochkin","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Laboratory of Cardiac Electrophysiology, National Medical Research Center for Cardiology, 121500 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-232X","authenticated-orcid":false,"given":"Olga S.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen 517182, China"},{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.bbrc.2005.05.054","article-title":"A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation","volume":"332","author":"Xia","year":"2005","journal-title":"Biochem. 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