{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:24:23Z","timestamp":1775751863498,"version":"3.50.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,3,16]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes,\n            <jats:italic>KVLQT1,<\/jats:italic>\n            <jats:italic>KCNE1<\/jats:italic>\n            (\n            <jats:italic>minK<\/jats:italic>\n            ), and\n            <jats:italic>HERG<\/jats:italic>\n            , and the cardiac sodium channel gene\n            <jats:italic>SCN5A<\/jats:italic>\n            cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in\n            <jats:italic>KVLQT1<\/jats:italic>\n            and\n            <jats:italic>KCNE1<\/jats:italic>\n            in JLNS families in which QTc prolongation was inherited as a dominant trait.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of\n            <jats:italic>KVLQT1<\/jats:italic>\n            was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in\n            <jats:italic>KVLQT1<\/jats:italic>\n            and has deleterious effects on the\n            <jats:italic>KVLQT1<\/jats:italic>\n            potassium channel, causing a frameshift and the truncation of the\n            <jats:italic>KVLQT1<\/jats:italic>\n            protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014A novel homozygous\n            <jats:italic>KVLQT1<\/jats:italic>\n            mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.10.1344","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1344-1347","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Homozygous Deletion in\n            <i>KVLQT1<\/i>\n            Associated With Jervell and Lange-Nielsen Syndrome"],"prefix":"10.1161","volume":"99","author":[{"given":"Qiuyun","family":"Chen","sequence":"first","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Gingell","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur J.","family":"Moss","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Napolitano","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia G.","family":"Priori","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Kehoe","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Schulze-Bahr","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Towbin","sequence":"additional","affiliation":[{"name":"From the Departmentx of Pediatrics (Cardiology) (Q.C., D.Z., Q.W., J.A.T.) and Molecular and Human Genetics (J.A.T.), Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, Tex; Children\u2019s Hospital at Buffalo, Buffalo, NY (R.L.G.); Department of Medicine (A.J.M., E.K., J.L.R.,) and Department of Community and Preventive Medicine (J.L.R.), University of Rochester Medical Center, Rochester, NY; Department of Cardiology, University of Pavia, and Policlinico S. Matteo, IFCCS, Pavia, Italy (C.N...."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"378","volume":"109","year":"1975","unstructured":"Schwartz PJ, Periti M, Malliani A. The long QT syndrome. Am Heart J. 1975;109:378\u2013390.","journal-title":"Am Heart J"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.84.3.1136"},{"key":"e_1_3_2_3_2","first-page":"656","volume":"45","year":"1963","unstructured":"Romano C, Gemme G, Pongiglione R. Arthmie cardiache rare dell\u2019eta pediatricia, II: accessi sincopali per fibrillazione ventricolare parossistica. Clin Pediatr. 1963;45:656\u2013661.","journal-title":"Clin Pediatr"},{"key":"e_1_3_2_4_2","first-page":"103","volume":"54","year":"1964","unstructured":"Ward OC. A new familial cardiac syndrome in children. J Irish Med Assoc. 1964;54:103\u2013106.","journal-title":"J Irish Med Assoc"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(57)90079-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1673802"},{"key":"e_1_3_2_7_2","first-page":"1335","volume":"49","year":"1991","unstructured":"Keating MT, Atkinson D, Dunn C, Timothy K, Vincent GM, Leppert M. Consistent linkage of the long QT syndrome to the Harvey ras-1 locus on chromosome 11. Am J Hum Genet. 1991;49:1335\u20131339.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.6.7994803"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-141"},{"key":"e_1_3_2_10_2","first-page":"1114","volume":"57","year":"1995","unstructured":"Schott J, Charpentier F, Peltier S, Foley P, Drouin E, Bonheur J, Donnelly P, Vergnaud G, Bachner L, Moisan J, Marec HL, Pascal O. Mapping of a gene for long QT syndrome to chromosome 4q25\u201327. Am J Hum Genet. 1995;57:1114\u20131122.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-17"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90358-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90359-3"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-338"},{"key":"e_1_3_2_15_2","first-page":"412","volume":"259","year":"1978","unstructured":"Levine SA, Woodworth CR. Congenital deaf-mutism, prolonged Q-T interval, syncopal attacks and sudden death. N Engl J Med. 1978;259:412\u2013417.","journal-title":"N Engl J Med"},{"key":"e_1_3_2_16_2","first-page":"361","volume":"33","year":"1964","unstructured":"Fraser GR, Froggatt P, James TN. Congenital deafness associated with electrocardiographic abnormalities, fainting attacks and sudden death. Q J Med. 1964;33:361\u2013385.","journal-title":"Q J Med"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1964.tb00469.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-186"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705293362204"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-267"},{"key":"e_1_3_2_21_2","first-page":"353","volume":"7","year":"1920","unstructured":"Bazett HC. An analysis of the time-relationships of electrocardiograms. Heart. 1920;7:353\u2013370.","journal-title":"Heart"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02619631"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.17.5472"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.3.565"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.9.2778"},{"key":"e_1_3_2_26_2","first-page":"2179","volume":"12","year":"1997","unstructured":"Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JFN, Bathen J, Aslaksen B, Sorland SJ, Lund O, Malcolm S, Penbrey M, Bhattcharya S, Bitner-Glindziaz M. Isk and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum Molec Genet. 1997;12:2179\u20132185.","journal-title":"Hum Molec Genet"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209173271204"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.99.10.1344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:56:22Z","timestamp":1715532982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.99.10.1344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3,16]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1999,3,16]]}},"alternative-id":["10.1161\/01.CIR.99.10.1344"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.99.10.1344","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3,16]]},"assertion":[{"value":"1998-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}