{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T16:20:22Z","timestamp":1756311622441},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2011,2]]},"abstract":"\n Background\u2014<\/jats:title>\n \n Mutations in\n KCNJ2<\/jats:italic>\n , the gene encoding the human inward rectifier potassium channel Kir2.1 (I\n K1<\/jats:sub>\n or I\n Kir2.1<\/jats:sub>\n ), have been identified in Andersen-Tawil syndrome. Andersen-Tawil syndrome is a multisystem inherited disease exhibiting periodic paralysis, cardiac arrhythmias, and dysmorphic features at times mimicking catecholaminergic polymorphic ventricular tachycardia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results\u2014<\/jats:title>\n \n Our proband displayed dysmorphic features including micrognathia, clinodactyly, and syndactyly and exhibited multiform extrasystoles and bidirectional ventricular tachycardia both at rest and during exercise testing. The patient's symptoms continued after administration of nadolol but subsided after treatment with flecainide. Molecular genetic screening revealed a novel heterozygous mutation (c.779G>C\/p.R260P) in\n KCNJ2<\/jats:italic>\n . Whole-cell patch-clamp studies conducted in TSA201 cells transfected with wild-type human\n KCNJ2<\/jats:italic>\n cDNA (WT-\n KCNJ2<\/jats:italic>\n ) yielded robust I\n Kir2.1<\/jats:sub>\n but no measurable current in cells expressing the R260P mutant. Coexpression of WT and R260P-\n KCNJ2<\/jats:italic>\n (heterozygous expression) yielded a markedly reduced inward I\n Kir2.1<\/jats:sub>\n compared with WT alone (\u221236.5\u00b19.8 pA\/pF versus \u2212143.5\u00b111.4 pA\/pF, n=8 for both,\n P<\/jats:italic>\n <0.001, respectively, at \u221290 mV), indicating a strong dominant negative effect of the mutant. The outward component of I\n Kir2.1<\/jats:sub>\n measured at \u221250 mV was also markedly reduced with the heterozygous expression versus WT (0.52\u00b15.5 pA\/pF versus 23.4\u00b16.7 pA\/pF, n=8 for both,\n P<\/jats:italic>\n <0.001, respectively). Immunocytochemical analysis indicates that impaired trafficking of R260P-\n KCNJ2<\/jats:italic>\n channels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions\u2014<\/jats:title>\n \n We report a novel de novo\n KCNJ2<\/jats:italic>\n mutation associated with classic phenotypic features of Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry. The R260P mutation produces a strong dominant negative effect leading to marked suppression of I\n K1<\/jats:sub>\n secondary to a trafficking defect.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circgenetics.110.957696","type":"journal-article","created":{"date-parts":[[2010,12,11]],"date-time":"2010-12-11T03:30:48Z","timestamp":1292038248000},"page":"51-57","source":"Crossref","is-referenced-by-count":30,"title":["Biophysical and Molecular Characterization of a Novel De Novo\n KCNJ2<\/i>\n Mutation Associated With Andersen-Tawil Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia Mimicry"],"prefix":"10.1161","volume":"4","author":[{"given":"Hector","family":"Barajas-Martinez","sequence":"first","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Ontiveros","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Caceres","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayurika","family":"Desai","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Burashnikov","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Scaglione","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Antzelevitch","sequence":"additional","affiliation":[{"name":"From the Masonic Medical Research Laboratory (H.B.-M., D.H., G.O., G.C., M.D., E.B., C.A.), Utica, NY; and Fundacion para la Prevencion de la Muerte Subita-FEPREMUS and Centro de Estudios Geneticos (G.O., J.S.), Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1971.tb06990.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350313"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420306"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00342-7"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990716)85:2<147::AID-AJMG9>3.0.CO;2-0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2006.03.025"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circep.109.872309"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.172619"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.829192"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/362127a0"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15183"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000072261.14060.47"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310278200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00725-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.4161\/chan.4770"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060653d"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/17431380410032490"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.104.472498"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.2"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9483"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000218214.64942.64"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.07.010"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2005.11.026"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.04.028"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091193"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2008.02.023"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eun180"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1942"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.10.005"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004021107"}],"container-title":["Circulation: Cardiovascular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGENETICS.110.957696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:46:32Z","timestamp":1715564792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGENETICS.110.957696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1161\/CIRCGENETICS.110.957696"],"URL":"https:\/\/doi.org\/10.1161\/circgenetics.110.957696","relation":{},"ISSN":["1942-325X","1942-3268"],"issn-type":[{"value":"1942-325X","type":"print"},{"value":"1942-3268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2]]}}}