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Itoh, H.* ; Crotti, L. ; Aiba, T.* ; Spazzolini, C.* ; Denjoy, I.* ; Fressart, V.* ; Hayashi, K.* ; Nakajima, T.* ; Ohno, S.* ; Makiyama, T.* ; Wu, J.* ; Hasegawa, K.* ; Mastantuono, E. ; Dagradi, F.* ; Pedrazzini, M.* ; Yamagishi, M.* ; Berthet, M.* ; Murakami, Y.* ; Shimizu, W.* ; Guicheney, P.* ; Schwartz, P.J.* ; Horie, M.*

The genetics underlying acquired long QT syndrome: Impact for genetic screening.

Eur. Heart J. 37, 1456-1464 (2016)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
AIMS: Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors. METHODS AND RESULTS: We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated 'true aLQTS' (QTc within normal limits) or 'unmasked cLQTS' (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in 'true aLQTS', KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7-41%] vs. 64% [95% CI 43-82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations. CONCLUSION: A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acquired Long Qt Syndrome ; Congenital Long Qt Syndrome ; Drug-induced Long Qt Syndrome ; Genetics; Torsades-de-pointes; Variants; Mutation; Prolongation; Polymorphism; Interval; Kcne1; Association; Population; Herg
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Zeitschrift European Heart Journal
Quellenangaben Band: 37, Heft: 18, Seiten: 1456-1464 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.1093/eurheartj/ehv695
WOS ID WOS:000375404500011
Scopus ID 84975852981
PubMed ID 26715165
Erfassungsdatum 2016-01-01
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