{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T16:11:35Z","timestamp":1756311095364},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Mutations in\n              <jats:italic>KCNJ2<\/jats:italic>\n              , a gene encoding the inward rectifier K\n              <jats:sup>+<\/jats:sup>\n              channel Kir2.1, are associated with Andersen-Tawil syndrome (ATS), which is characterized by (1) ventricular tachyarrhythmias associated with QT (QU)-interval prolongation, (2) periodic paralysis, and (3) dysmorphic features.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We identified a novel\n              <jats:italic>KCNJ2<\/jats:italic>\n              mutation, S369X, in a 13-year-old boy with prominent QU-interval prolongation and mild periodic paralysis. The mutation results in the truncation at the middle of the cytoplasmic C-terminal domain that eliminates the endoplasmic reticulum (ER)-to-Golgi export signal. Current recordings from Chinese hamster ovary cells transfected with\n              <jats:italic>KCNJ2<\/jats:italic>\n              -S369X exhibited significantly smaller K\n              <jats:sup>+<\/jats:sup>\n              currents compared with\n              <jats:italic>KCNJ2<\/jats:italic>\n              wild type (WT) (1 \u03bcg each) (\u221284\u00b114 versus \u2212542\u00b146 picoamperes per picofarad [pA\/pF]; \u2212140 mV;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). Coexpression of the WT and S369X subunits did not show a dominant-negative suppression effect but yielded larger currents than those of WT+S369X (\u2212724\u00b198 pA\/pF&gt;\u2212[84+542] pA\/pF; 1 \u03bcg each; \u2212140 mV). Confocal microscopy analysis showed that the fluorescent protein-tagged S369X subunits were predominantly retained in the ER when expressed alone; however, the expression of S369X subunits to the plasma membrane was partially restored when coexpressed with WT. Fluorescence resonance energy transfer analysis demonstrated direct protein-protein interactions between WT and S369X subunits in the intracellular compartment.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The S369X mutation causes a loss of the ER export motif. However, the trafficking deficiency can be partially rescued by directly assembling with the WT protein, resulting in a limited restoration of plasma membrane localization and channel function. This alleviation may explain why our patient presented with a relatively mild ATS phenotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.110.958157","type":"journal-article","created":{"date-parts":[[2011,4,15]],"date-time":"2011-04-15T03:01:16Z","timestamp":1302836476000},"page":"253-260","source":"Crossref","is-referenced-by-count":17,"title":["A Novel\n            <i>KCNJ2<\/i>\n            Nonsense Mutation, S369X, Impedes Trafficking and Causes a Limited Form of Andersen-Tawil Syndrome"],"prefix":"10.1161","volume":"4","author":[{"given":"Takahiro","family":"Doi","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeru","family":"Makiyama","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Morimoto","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshisumi","family":"Haruna","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Tsuji","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Akao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (T.D., T. Makiyama, Y.H., K.T., S.O., T.K.) and Center for Medical Education (T. Morimoto), Kyoto University, Graduate School of Medicine, Kyoto, Japan; Department of Cardiovascular Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); Takahashi Clinic for Pediatric Cardiology, Otsu, Japan (Y.T.); and Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.)."}],"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":"10.1002\/(SICI)1096-8628(19990716)85:2<147::AID-AJMG9>3.0.CO;2-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00342-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15183"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000072261.14060.47"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90021-7"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199412000-00024"},{"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":"10.1146\/annurev.physiol.59.1.171"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000019906.35135.a3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00046-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.05.011"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9483"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/342360"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310278200"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.081620"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00725-0"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/circep.109.872309"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.104.472498"},{"key":"e_1_3_4_23_2","first-page":"2","article-title":"Recommendations guiding physicians in biomedical research involving human subjects","volume":"35","author":"World Medical Association Declaration of Helsinki","year":"1997","unstructured":"World Medical Association Declaration of Helsinki. 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