Prevalence study of genetically defined skeletal muscle channelopathies in England
Prevalence study of genetically defined skeletal muscle channelopathies in England
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DOI：
10.1212/wnl.0b013e31828cf8d0
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发表时间：
2013-04-01
期刊：
影响因子：
9.9
通讯作者：
Hanna, Michael G.
中科院分区：
文献类型：
--
作者：
Horga, Alejandro;Rayan, Dipa L. Raja;Hanna, Michael G.
目的：为了获得骨骼肌channelopathies的最低点患病率，并评估与这些disorder.Methods相关的突变的频率分布：人口统计学，临床，电生理学和遗传学数据的分析，在我们的国家专家channelopathy服务评估的所有患者。只有生活在英国的非营养不良性肌强直或周期性麻痹的基因诊断患者才有资格参加这项研究。结果：共665例患者符合纳入标准，其中593例居住在英国，最低患病率为1.12/10万（95%可信区间[CI] 1.03-1.21）。特定疾病的患病率数据如下：先天性肌强直0.52/10万（95% CI 0.46-0.59），先天性副肌强直0.17/100，000（95% CI 0.13-0.20），钠通道肌强直0.06/100，000（95% CI 0.04-0.08），高钾型周期性麻痹0.17/100，000（95% CI 0.13-0.20），低钾型周期性麻痹0.13/100，000（95% CI 0.10-0.17），Andersen-Tawil综合征（ATS）0.08/100，000（95% CI 0.05-0.10）。在整个样本中在665例患者中，104种不同的CLCN 1突变中有15种突变占所有先天性肌强直患者的60%，22种SCN 4A突变中有11种突变占86%的先天性副肌强直/钠通道肌强直家系，17种KCNJ 2突变中有3种突变占42%的ATS家系。我们描述的第一次在英国的遗传定义的骨骼肌通道病的总体患病率。尽管在非营养不良性肌强直和ATS患者中观察到大量的突变，但数量有限的病例占很大比例。
Objectives: To obtain minimum point prevalence rates for the skeletal muscle channelopathies and to evaluate the frequency distribution of mutations associated with these disorders.Methods: Analysis of demographic, clinical, electrophysiologic, and genetic data of all patients assessed at our national specialist channelopathy service. Only patients living in the United Kingdom with a genetically defined diagnosis of nondystrophic myotonia or periodic paralysis were eligible for the study. Prevalence rates were estimated for England, December 2011.Results: A total of 665 patients fulfilled the inclusion criteria, of which 593 were living in England, giving a minimum point prevalence of 1.12/100,000 (95% confidence interval [CI] 1.03-1.21). Disease-specific prevalence figures were as follows: myotonia congenita 0.52/100,000 (95% CI 0.46-0.59), paramyotonia congenita 0.17/100,000 (95% CI 0.13-0.20), sodium channel myotonias 0.06/100,000 (95% CI 0.04-0.08), hyperkalemic periodic paralysis 0.17/100,000 (95% CI 0.13-0.20), hypokalemic periodic paralysis 0.13/100,000 (95% CI 0.10-0.17), and Andersen-Tawil syndrome (ATS) 0.08/100,000 (95% CI 0.05-0.10). In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees.Conclusion: We describe for the first time the overall prevalence of genetically defined skeletal muscle channelopathies in England. Despite the large variety of mutations observed in patients with nondystrophic myotonia and ATS, a limited number accounted for a large proportion of cases.