{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:32:20Z","timestamp":1791048740802,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Long-QT syndrome (LQTS) is an inherited disorder associated with sudden cardiac death. The cytoskeletal protein syntrophin-\u03b1\n                    <jats:sub>1<\/jats:sub>\n                    (SNTA1) is known to interact with the cardiac sodium channel (hNa\n                    <jats:sub>v<\/jats:sub>\n                    1.5), and we hypothesized that SNTA1 mutations might cause phenotypic LQTS in patients with genotypically normal hNa\n                    <jats:sub>v<\/jats:sub>\n                    1.5 by secondarily disturbing sodium channel function.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Mutational analysis of\n                    <jats:italic>SNTA1<\/jats:italic>\n                    was performed on 39 LQTS patients (QTc\u2265480 ms) with previously negative genetic screening for the known LQTS-causing genes. We identified a novel A257G-\n                    <jats:italic>SNTA1<\/jats:italic>\n                    missense mutation, which affects a highly conserved residue, in 3 unrelated LQTS probands but not in 400 ethnic-matched control alleles. Only 1 of these probands had a preexisting family history of LQTS and sudden death with an additional intronic variant in KCNQ1. Electrophysiological analysis was performed using HEK-293 cells stably expressing hNa\n                    <jats:sub>v<\/jats:sub>\n                    1.5 and transiently transfected with either wild-type or mutant SNTA1 and, in neonatal rat cardiomyocytes, transiently transfected with either wild-type or mutant SNTA1. In both HEK-293 cells and neonatal rat cardiomyocytes, increased peak sodium currents were noted along with a 10-mV negative shift of the onset and peak of currents of the current-voltage relationships. In addition, A257G-SNTA1 shifted the steady-state activation (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>h<\/jats:sub>\n                    ) leftward by 9.4 mV, whereas the voltage-dependent inactivation kinetics and the late sodium currents were similar to wild-type SNTA1.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusion\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:italic>SNTA1<\/jats:italic>\n                    is a new susceptibility gene for LQTS. A257G-\n                    <jats:italic>SNTA1<\/jats:italic>\n                    can cause gain-of-function of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 similar to the LQT3.\n                  <\/jats:p>","DOI":"10.1161\/circep.108.769224","type":"journal-article","created":{"date-parts":[[2008,5,28]],"date-time":"2008-05-28T21:57:48Z","timestamp":1212011868000},"page":"193-201","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["\u03b1-1-Syntrophin Mutation and the Long-QT Syndrome"],"prefix":"10.1161","volume":"1","author":[{"given":"Geru","family":"Wu","sequence":"first","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ai","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyalaxmi","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutao","family":"Xi","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Li","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Abbasi","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enkhsaikhan","family":"Purevjav","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveh","family":"Samani","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Ackerman","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Qi","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"Moss","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Shimizu","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Towbin","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Vatta","sequence":"additional","affiliation":[{"name":"From the Electrophysiology Research Laboratory, Texas Heart Institute\/St. Luke\u2019s Episcopal Hospital, Houston, Tex (G.W., T.A., Y.X., S.A., K.S., J.C.); Pediatric Cardiology, Texas Children\u2019s Hospital\/Baylor College of Medicine, Houston, Tex (J.J.K., B.M., Z.L., E.P., J.A.T., M.V.); Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics\/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minn (M.J.A.); Heart Research Follow-up..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.104.494476"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.01.006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01335"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0239"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.635268"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2006.11.030"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.05.020"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710527105"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2000.tb00016.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90157-M"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.43.25859"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4446"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37566-X"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000439200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00128.1998"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209938200"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.2.8339437"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2007.00777.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.10.2929"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000237466.13252.5e"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13200"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9136"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.676783"}],"container-title":["Circulation: Arrhythmia and Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCEP.108.769224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T19:23:56Z","timestamp":1715541836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCEP.108.769224"}},"subtitle":["A Disease of Sodium Channel Disruption"],"short-title":[],"issued":{"date-parts":[[2008,8]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1161\/CIRCEP.108.769224"],"URL":"https:\/\/doi.org\/10.1161\/circep.108.769224","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1120383.576560","asserted-by":"object"}]},"ISSN":["1941-3149","1941-3084"],"issn-type":[{"value":"1941-3149","type":"print"},{"value":"1941-3084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8]]},"assertion":[{"value":"2008-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}