Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
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转诊进行 FAMILION 长 QT 综合征基因检测的前 2,500 名连续无关患者的突变谱和患病率。
DOI：
10.1016/j.hrthm.2009.05.021
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发表时间：
2009-09
期刊：
影响因子：
5.5
通讯作者：
Ackerman, Michael J.
中科院分区：
文献类型：
--
作者：
Kapplinger, Jamie D.;Tester, David J.;Salisbury, Benjamin A.;Carr, Janet L.;Harris-Kerr, Carole;Pollevick, Guido D.;Wilde, Arthur A. M.;Ackerman, Michael J.
长QT综合征(LQTS)是一种潜在的致命性、高度可治疗的心脏通道病，其基因检测从发现到翻译已经成熟，现在已经在临床上应用。在这里，我们检查了在FAMILION®LQTS临床基因检测中发现的前2,500例无关病例中发现的突变的频谱和流行率。对前2,500例患者(女性患者1,515例，平均年龄23±17岁，范围0-90岁)进行了5个LQTS易感基因突变扫描：KCNQ1(LQT1)、KCNH2(LQT2)、SCN5A(LQT3)、KCNE1(LQT5)和KCNE2(LQT6)。总体而言，903例(36%)转介病例存在可能的LQTS引起的突变，该突变在2600个参考等位基因中缺失；821例(91%)突变阳性病例为单一基因型，其余82例(9%)≥1基因存在>；1突变，包括52例具有>；1基因突变的复合杂合子。在562个突变中，错义突变394个(70%)，一次突变428个(76%)，新突变336个(60%)，其中KCNQ1突变92个，KCNH2突变159个，SCN5A突变70个。这一队列使可公开获得的LQTS相关突变简编增加了50%，最近检测到的大约三分之一的突变仍然是新的。尽管对照人群数据表明，这些突变中的绝大多数是致病的，但对基因测试结果的专家解释对于LQTS基因测试结果的有效临床应用仍然至关重要。
Long QT syndrome (LQTS) is a potentially lethal, highly treatable cardiac channelopathy for which genetic testing has matured from discovery to translation and now clinical implementation. Here we examine the spectrum and prevalence of mutations found in the first 2,500 unrelated cases referred for the FAMILION® LQTS clinical genetic test. Retrospective analysis of the first 2,500 cases (1,515 female patients, average age at testing 23 ± 17 years, range 0 to 90 years) scanned for mutations in 5 of the LQTS-susceptibility genes: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). Overall, 903 referral cases (36%) hosted a possible LQTS-causing mutation that was absent in >2,600 reference alleles; 821 (91%) of the mutation-positive cases had single genotypes, whereas the remaining 82 patients (9%) had >1 mutation in ≥1 gene, including 52 cases that were compound heterozygous with mutations in >1 gene. Of the 562 distinct mutations, 394 (70%) were missense, 428 (76%) were seen once, and 336 (60%) are novel, including 92 of 199 in KCNQ1, 159 of 226 in KCNH2, and 70 of 110 in SCN5A. This cohort increases the publicly available compendium of putative LQTS-associated mutations by >50%, and approximately one-third of the most recently detected mutations continue to be novel. Although control population data suggest that the great majority of these mutations are pathogenic, expert interpretation of genetic test results will remain critical for effective clinical use of LQTS genetic test results.
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影响因子：
5.5
作者：
Tester, David J.;Cronk, Lisa B.;Ackerman, Michael J.
通讯作者：
Ackerman, Michael J.
影响因子：
120.7
作者：
Napolitano, C;Priori, SG;Leonardi, S
通讯作者：
Leonardi, S
影响因子：
4.4
作者：
Splawski, I;Shen, JX;Keating, MT
通讯作者：
Keating, MT
DOI：
10.1073/pnas.0710527105
发表时间：
2007-12-26
影响因子：
11.1
作者：
Chen, Lei;Marquardt, Michelle L.;Kass, Robert S.
通讯作者：
Kass, Robert S.
影响因子：
82.9
作者：
Ackerman, MJ
通讯作者：
Ackerman, MJ