Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity
Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity
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DOI：
10.1080/17431380410032490
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Ptacek, LJ
中科院分区：
文献类型：
--
作者：
Donaldson, MR;Yoon, G;Ptacek, LJ
Andersen-Tawil综合征（ATS）由于其多样和可变的表型，在通道病领域占有独特的地位。ATS患者通常表现为周期性麻痹、心律失常和发育畸形三联征。虽然ATS的发病率很高，但疾病的表达和严重程度是显著可变的。KCNJ 2基因突变是ATS的主要病因，在30个家系中发现了21个突变。这些突变通过异质性机制影响通道功能，包括降低PIP 2相关通道激活和改变孔功能。除了基于KCNJ 2的ATS外，近40%病例的遗传基础尚不清楚。其他ATS基因可能与Kir2.1共享共同的途径或功能，或促进该离子通道的活性。在这篇综述中，我们探讨解释ATS的发病机制，表达和变异性的假说。
Due to its varied and variable phenotypes, Andersen-Tawil syndrome (ATS) holds a unique place in the field of channelopathies. Patients with ATS typically present with the triad of periodic paralysis, cardiac arrhythmias, and developmental dysmorphisms. Although penetrance of ATS is high, disease expression and severity are remarkably variable. Mutations in KCNJ2 are the primary cause of ATS with 21 mutations discovered in 30 families. These mutations affect channel function through heterogeneous mechanisms, including reduced PIP2-related channel activation and altered pore function. Aside from KCNJ2-based ATS, the genetic basis of this disease in nearly 40% of cases is unknown. Other ATS genes likely share a common pathway or function with Kir2.1 or facilitate the activity of this ion channel. In this review, we explore hypotheses explaining the pathogenesis, expression, and variability of ATS.