A Common Mutation of Long QT Syndrome Type 1 in Japan
A Common Mutation of Long QT Syndrome Type 1 in Japan
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DOI：
10.1253/circj.cj-15-0342
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发表时间：
2015-09-01
影响因子：
3.3
通讯作者：
Horie, Minoru
中科院分区：
文献类型：
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作者：
Itoh, Hideki;Dochi, Kenichi;Horie, Minoru
背景资料：以往的长QT综合征（LQTS）研究揭示了KCNQ 1突变中存在国家特异性热点，本研究的目的是评估一种常见突变对日本LQT 1患者临床表型的影响。方法和结果：我们回顾性研究了190例LQT 1日本先证者的每种突变频率，并评估了LQT 1携带者的临床严重程度，突变我们还将其与携带其他突变的携带者进行了比较。在日本队列中，最常见的突变是p.A344spl（c.1032 G> A），包括外显子7最后一个碱基的鸟嘌呤取代腺嘌呤，在17个先证者中发现（8.9%）。关于A344 spl携带者的临床特征，平均发病年龄为10+/-4岁，> 40%有症状，平均校正QT间期为461 ± 30 ms。A344 spl突变携带者（n= 31）的预后介于A341 V突变报告的与严重表型相关的患者（n= 24）之间。结论：A344 spl突变是日本常见的LQTS基因型，在研究LQT 1临床表型时应考虑国家特异性热点的影响。
Background: Previous studies of long QT syndrome (LQTS) have revealed the presence of country-specific hot spots in KCNQ1 mutations, and the purpose of this study was to evaluate the influence of a common mutation on clinical phenotypes in Japanese LQT1 patients.Methods and Results: We retrospectively studied the frequency of each mutation in 190 LQT1 Japanese probands and evaluated the clinical severity of LQT1 among carriers with a common mutation. We also compared it with that of carriers with other mutations. In the Japanese cohort, the most common mutation was p. A344spl (c.1032 G> A), comprising a substitution of a guanine for an adenine at the last base of exon 7, and it was found in 17 probands (8.9%). Regarding the clinical characteristics of A344spl carriers, the mean age-of-onset was 10+/-4 years, > 40% were symptomatic, and the mean corrected QT interval was 461+/-30 ms. The prognosis for carriers of the A344spl mutation (n= 31) was intermediate between that for the A341V mutation reported to be associated with severe phenotypes (n= 24) and other mutations (n= 290).Conclusions: The A344spl mutation was a frequent LQTS genotype in Japan, which indicates that the influence of country-specific hot spots should be considered when studying LQT1 clinical phenotypes.