{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:03:39Z","timestamp":1789506219257,"version":"build-2803163510"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1997,11,4]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            <jats:italic>KVLQT1<\/jats:italic>\n            , the gene encoding the \u03b1-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhythmias leading to recurrent syncopes and sudden death. However, there is considerable variability in the clinical presentation, and potential severity is often difficult to evaluate. To analyze the relationship between phenotypes and underlying defects in\n            <jats:italic>KVLQT1<\/jats:italic>\n            , we investigated mutations in this gene in 20 RWS families originating from France.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            By PCR-SSCP analysis, 16 missense mutations were identified in\n            <jats:italic>KVLQT1<\/jats:italic>\n            , 11 of them being novel. Fifteen mutations, localized in the transmembrane domains S2-S3, S4-S5, P, and S6, were associated with a high percentage of symptomatic carriers (55 of 95, or 58%) and sudden deaths (23 of 95, or 24%). In contrast, a missense mutation, Arg\n            <jats:sup>555<\/jats:sup>\n            Cys, identified in the C-terminal domain in 3 families, was associated with a significantly less pronounced QT prolongation (459\u00b133 ms, n=41, versus 480\u00b132 ms, n=70,\n            <jats:italic>P<\/jats:italic>\n            =.0012), and significantly lower percentages of symptomatic carriers (7 of 44, or 16%,\n            <jats:italic>P<\/jats:italic>\n            &lt;.001) and sudden deaths (2 of 44, or 5%,\n            <jats:italic>P<\/jats:italic>\n            &lt;.01). Most of the cardiac events occurring in these 3 families were triggered by drugs known to affect ventricular repolarization.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            Our data show a wide KVLQT1 allelic heterogeneity among 20 families in which KVLQT1 causes RWS. We describe the first missense mutation in the C-terminal domain of KVLQT1, which is clearly associated with a fruste phenotype, which could be a favoring factor of acquired LQT syndrome.\n          <\/jats:p>","DOI":"10.1161\/01.cir.96.9.2778","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"2778-2781","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":264,"title":["<i>KVLQT1<\/i>\n            C-Terminal Missense Mutation Causes a Forme Fruste Long-QT Syndrome"],"prefix":"10.1161","volume":"96","author":[{"given":"Claire","family":"Donger","sequence":"first","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Denjoy","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Berthet","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Neyroud","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Cruaud","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Bennaceur","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Chivoret","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketty","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Coumel","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Guicheney","sequence":"additional","affiliation":[{"name":"From INSERM U153, Groupe Hospitalier Pitie\u0301-Salpe\u0302trie\u0300re, Institut de Myologie, Paris (C.D., M.B., N.N., M.B., K.S., P.G.) and Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D., N.N., P.C.) Paris; Cha\u0302teau des Co\u0302tes, Les Loges en Josas (I.D.); Ge\u0301ne\u0301thon-CNRS URA 1922, Evry (C.C.); and Service de Cardiologie, Ho\u0302pital de Brabois, Nancy (G.C.), France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(96)80010-4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-17"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-186"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705293362204"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.8.1996"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.9.1319"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.7.567"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.3.565"},{"key":"e_1_3_2_9_2","first-page":"353","volume":"7","year":"1920","unstructured":"Bazett H. An analysis of the time relations of electrocardiograms. Heart. 1920;7:353-367.","journal-title":"Heart"},{"key":"e_1_3_2_10_2","unstructured":"Moss AJ Robinson J. Clinical features of the idiopathic long QT syndrome. 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