{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:23:06Z","timestamp":1790734986143,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>KCNQ1 mutations cause QTc prolongation increasing life-threatening arrhythmias risks. Heterozygous mutations [type 1 long QT syndrome (LQT1)] are common. Homozygous KCNQ1 mutations cause type 1 Jervell and Lange\u2013Nielsen syndrome (JLNS) with deafness and higher sudden cardiac death risk. KCNQ1 variants causing JLNS or LQT1 might have distinct phenotypic expressions in heterozygous patients. The aim of this study is to evaluate QTc duration and incidence of long QT syndrome\u2013related cardiac events according to genetic presentation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We enrolled LQT1 or JLNS patients with class IV\/V KCNQ1 variants from our inherited arrhythmia clinic (September 1993 to January 2023). Medical history, ECG, and follow-up were collected. Additionally, we conducted a thorough literature review for JLNS variants. Survival curves were compared between groups, and multivariate Cox regression models identified genetic and clinical risk factors. Among the 789 KCNQ1 variant carriers, 3 groups were identified: 30 JLNS, 161 heterozygous carriers of JLNS variants (HTZ-JLNS), and 550 LQT1 heterozygous carriers of non-JLNS variants (HTZ-Non-JLNS). At diagnosis, mean age was 3.4 \u00b1 4.7 years for JLNS, 26.7 \u00b1 21 years for HTZ-JLNS, and 26 \u00b1 21 years for HTZ-non-JLNS; 55.3% were female; and the mean QTc was 551 \u00b1 54\u2005ms for JLNS, 441 \u00b1 32\u2005ms for HTZ-JLNS, and 467 \u00b1 36\u2005ms for HTZ-Non-JLNS. Patients with heterozygous JLNS mutations (HTZ-JLNS) represented 22% of heterozygous KCNQ1 variant carriers and had a lower risk of cardiac events than heterozygous non-JLNS variant carriers (HTZ-Non-JLNS) [hazard ratio (HR) = 0.34 (0.22\u20130.54); P &amp;lt; 0.01]. After multivariate analysis, four genetic parameters were independently associated with events: haploinsufficiency [HR = 0.60 (0.37\u20130.97); P = 0.04], pore localization [HR = 1.61 (1.14\u20131.2.26); P &amp;lt; 0.01], C-terminal localization [HR = 0.67 (0.46\u20130.98); P = 0.04], and group [HR = 0.43 (0.27\u20130.69); P &amp;lt; 0.01].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other LQT1 patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euae136","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T14:51:51Z","timestamp":1717426311000},"source":"Crossref","is-referenced-by-count":14,"title":["Genetic characterization of <i>KCNQ1<\/i> variants improves risk stratification in type 1 long QT syndrome patients"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5185-8563","authenticated-orcid":false,"given":"Charles","family":"Morgat","sequence":"first","affiliation":[{"name":"CNMR Maladies Cardiaques H\u00e9r\u00e9ditaires Rares, APHP, H\u00f4pital Bichat, 46 rue Henri Huchard , 75018 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4749-1428","authenticated-orcid":false,"given":"Ve\u0301ronique","family":"Fressart","sequence":"additional","affiliation":[{"name":"AP-HP, Service de Biochimie M\u00e9tabolique, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-8090","authenticated-orcid":false,"given":"Alessandra Pia","family":"Porretta","sequence":"additional","affiliation":[{"name":"CNMR Maladies Cardiaques H\u00e9r\u00e9ditaires Rares, APHP, H\u00f4pital Bichat, 46 rue Henri Huchard , 75018 Paris , France"},{"name":"Service of Cardiology, Centre Hospitalier Universitaire Vaudois , Lausanne , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Neyroud","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Research Unit on Cardiovascular and Metabolic Diseases, UMRS-1166 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Messali","sequence":"additional","affiliation":[{"name":"CNMR Maladies Cardiaques H\u00e9r\u00e9ditaires Rares, APHP, H\u00f4pital Bichat, 46 rue Henri Huchard , 75018 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Temmar","sequence":"additional","affiliation":[{"name":"AP-HP, Unit\u00e9 Rythmologie, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5971-1235","authenticated-orcid":false,"given":"Vincent","family":"Algalarrondo","sequence":"additional","affiliation":[{"name":"CNMR Maladies Cardiaques H\u00e9r\u00e9ditaires Rares, APHP, H\u00f4pital Bichat, 46 rue Henri Huchard , 75018 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-6351","authenticated-orcid":false,"given":"Elodie","family":"Surget","sequence":"additional","affiliation":[{"name":"CNMR Maladies Cardiaques H\u00e9r\u00e9ditaires Rares, APHP, H\u00f4pital Bichat, 46 rue Henri Huchard , 75018 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Bloch","sequence":"additional","affiliation":[{"name":"AP-HP, Service de Biochimie M\u00e9tabolique, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris , 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