Berge K E, Haugaa K H, Früh A, Anfinsen O-G, Gjesdal K, Siem G, Oyen N, Greve G, Carlsson A, Rognum T O, Hallerud M, Kongsgård E, Amlie J P, Leren T P
Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway.
Scand J Clin Lab Invest. 2008;68(5):362-8. doi: 10.1080/00365510701765643.
Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.
KCNQ1、HERG、SCN5A、minK和MiRP1基因的突变会导致长QT综合征（LQTS），该综合征有两种类型： Romano Ward综合征和Jervell和Lange-Nielsen综合征。我们对169名因Romano Ward综合征接受基因检测的无血缘关系患者以及13名因Jervell和Lange-Nielsen综合征接受基因检测的无血缘关系患者的LQTS相关基因进行了DNA测序。在这5个基因中总共鉴定出37种不同的突变，其中20种是新发现的。在符合Romano Ward综合征最严格临床标准的患者中，71%检测到了突变。在13名因Jervell和Lange-Nielsen综合征接受基因检测的无血缘关系患者中，有12名得到了分子遗传学诊断。对505名分子诊断明确的LQTS先证者亲属进行的级联基因筛查发现了251名突变携带者。观察到的外显率为41%。基于Jervell和Lange-Nielsen综合征患者的患病率，尽管必须谨慎，但挪威LQTS相关基因突变杂合子的患病率可能在1/100 - 1/300之间。
