{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:48:43Z","timestamp":1791809323061,"version":"4.3.4"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2002,1,22]]},"abstract":"\n \n \n \n Background<\/jats:italic>\n <\/jats:bold>\n \u2014\n <\/jats:italic>\n <\/jats:bold>\n Three distinct cardiac arrhythmia disorders, the long-QT syndrome, Brugada syndrome, and conduction system disease, have been associated with heterozygous mutations in the cardiac voltage-gated sodium channel \u03b1-subunit gene (\n SCN5A<\/jats:italic>\n ). We present clinical, genetic, and biophysical features of 2 new\n SCN5A<\/jats:italic>\n mutations that result in atrioventricular (AV) conduction block.\n <\/jats:p>\n \n \n \n \n Methods and Results<\/jats:italic>\n <\/jats:bold>\n \u2014\n <\/jats:italic>\n <\/jats:bold>\n SCN5A<\/jats:italic>\n was used as a candidate gene in 2 children with AV block. Molecular genetic studies revealed G to A transition mutations that resulted in the substitution of serine for glycine (G298S) in the domain I S5-S6 loop and asparagine for aspartic acid (D1595N) within the S3 segment of domain IV. The functional consequences of G298S and D1595N were assessed by whole-cell patch clamp recording of recombinant mutant channels coexpressed with the \u03b21 subunit in a cultured cell line (tsA201). Both mutations impair fast inactivation but do not exhibit sustained non-inactivating currents. The mutations also reduce sodium current density and enhance slower inactivation components. Action potential simulations predict that this combination of biophysical abnormalities will significantly slow myocardial conduction velocity.\n <\/jats:p>\n \n \n \n \n Conclusions<\/jats:italic>\n <\/jats:bold>\n \u2014\n <\/jats:italic>\n <\/jats:bold>\n A distinct pattern of biophysical abnormalities not previously observed for any other\n SCN5A<\/jats:italic>\n mutant have been recognized in association with AV block. These data provide insight into the distinct clinical phenotypes resulting from mutation of a single ion channel.\n <\/jats:p>","DOI":"10.1161\/hc0302.102592","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:07Z","timestamp":1027898167000},"page":"341-346","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":168,"title":["Clinical, Genetic, and Biophysical Characterization of\n SCN5A<\/i>\n Mutations Associated With Atrioventricular Conduction Block"],"prefix":"10.1161","volume":"105","author":[{"given":"Dao W.","family":"Wang","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (D.W.W., J.R.B., A.L.G.), Anesthesiology (P.C.V., J.R.B.), and Medicine (A.L.G.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics (D.W.B.), Medical University of South Carolina, Charleston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash C.","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W.W., J.R.B., A.L.G.), Anesthesiology (P.C.V., J.R.B.), and Medicine (A.L.G.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics (D.W.B.), Medical University of South Carolina, Charleston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Balser","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W.W., J.R.B., A.L.G.), Anesthesiology (P.C.V., J.R.B.), and Medicine (A.L.G.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics (D.W.B.), Medical University of South Carolina, Charleston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Alfred L.","family":"George","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W.W., J.R.B., A.L.G.), Anesthesiology (P.C.V., J.R.B.), and Medicine (A.L.G.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics (D.W.B.), Medical University of South Carolina, Charleston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Woodrow","family":"Benson","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W.W., J.R.B., A.L.G.), Anesthesiology (P.C.V., J.R.B.), and Medicine (A.L.G.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics (D.W.B.), Medical University of South Carolina, Charleston."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90359-3"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/32675"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/12618"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/376683a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.78.5.916"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00006-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.87.8.e37"},{"key":"e_1_3_2_9_2","unstructured":"McKusick-Nathans Institute for Genetic Medicine Johns Hopkins University (Baltimore MD) and National Center for Biotechnology Information National Library of Medicine (Bethesda MD). Online Mendelian Inheritance in Man OMIM (TM). Available at http:\/\/www.ncbi.nlm.nih.gov\/omim\/. Accessed December 5 2001."},{"key":"e_1_3_2_10_2","first-page":"1633","volume":"39","year":"1995","unstructured":"Brink PA, Ferreira A, Moolman JC, et al. Gene for progressive familial heart block type I maps to chromosome 19q13. Circulation. 1995; 39: 1633\u20131640.","journal-title":"Circulation"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35059090"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0236"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.74.6.1071"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.9.803"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.18.2466"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1952.sp004719"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.86.9.e91"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hc0302.102592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T01:40:21Z","timestamp":1715650821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hc0302.102592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1,22]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,1,22]]}},"alternative-id":["10.1161\/hc0302.102592"],"URL":"https:\/\/doi.org\/10.1161\/hc0302.102592","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1,22]]},"assertion":[{"value":"2002-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}