Phenotype Variability in Patients Carrying KCNJ2 Mutations
Phenotype Variability in Patients Carrying KCNJ2 Mutations
复制标题
携带 KCNJ2 突变的患者的表型变异
DOI：
10.1161/circgenetics.111.962316
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发表时间：
2012-06-01
影响因子：
--
通讯作者：
Horie, Minoru
中科院分区：
文献类型：
--
作者：
Kimura, Hiromi;Zhou, Jun;Horie, Minoru
KCNJ 2是编码人内向整流钾通道Kir2.1的基因，其突变可引起Andersen-Tawil综合征（ATS），这是一种表现出室性心律失常、周期性麻痹和畸形特征的疾病。然而，一些KCNJ 2突变携带者缺乏ATS三联体，有时共享儿茶酚胺能多态性室性心动过速（CPVT）的表型。我们调查了KCNJ 2突变携带者的临床和生物物理学特征。“方法和结果--在57个表现出典型（>= 2个ATS特征）和非典型（仅1个ATS特征或CPVT）ATS的无关先证者中进行KCNJ 2的突变分析。我们发现了24个变异携带者。在典型ATS、单纯心脏表型、周期性麻痹和CPVT中，突变阳性率分别为75%（15/20）、71%（5/7）、100%（2/2）和7%（2/28）。我们将所有携带者（n = 45，包括家族成员）分为2组：典型ATS（A）（n = 21，47%）和非典型表型（B）（n = 24，53%）。（A）中的患者具有较长的QUc间期[（A）：695 +/- 52 vs（B）：643 +/- 35 ms]和较高的U波振幅（0.24 +/- 0.07 vs 0.18 +/- 0.08 mV）。C端突变在（A）中更常见（85%对38%，P
Background-Mutations of KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features. However, some KCNJ2 mutation carriers lack the ATS triad and sometimes share the phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT). We investigated clinical and biophysical characteristics of KCNJ2 mutation carriers with "atypical ATS."Methods and Results-Mutational analyses of KCNJ2 were performed in 57 unrelated probands showing typical (>= 2 ATS features) and atypical (only 1 of the ATS features or CPVT) ATS. We identified 24 mutation carriers. Mutation-positive rates were 75% (15/20) in typical ATS, 71% (5/7) in cardiac phenotype alone, 100% (2/2) in periodic paralysis, and 7% (2/28) in CPVT. We divided all carriers (n = 45, including family members) into 2 groups: typical ATS (A) (n = 21, 47%) and atypical phenotype (B) (n = 24, 53%). Patients in (A) had a longer QUc interval [(A): 695 +/- 52 versus (B): 643 +/- 35 ms] and higher U-wave amplitude (0.24 +/- 0.07 versus 0.18 +/- 0.08 mV). C-terminal mutations were more frequent in (A) (85% versus 38%, P