英国的僵人综合征是由什么引起的？揭示常见和新的SCN4A突变。

What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed.

作者信息

Matthews E, Tan S V, Fialho D, Sweeney M G, Sud R, Haworth A, Stanley E, Cea G, Davis M B, Hanna M G

机构信息

Medical Research Council Centre for Neuromuscular Disease, Department of Molecular Neuroscience, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.

出版信息

Neurology. 2008 Jan 1;70(1):50-3. doi: 10.1212/01.wnl.0000287069.21162.94.

DOI:10.1212/01.wnl.0000287069.21162.94

PMID:18166706

Abstract

OBJECTIVE

To study the clinical and genetic features in a large cohort of UK patients with sodium channel paramyotonia congenita.

METHODS

We conducted a UK-wide clinical and molecular genetic study of patients presenting with a phenotype suggestive of paramyotonia congenita.

RESULTS

We identified 42 affected individuals (28 kindreds). All cases met our core criteria for a clinical diagnosis of paramyotonia congenita. Seventy-five percent of patients (32 patients/20 kindreds) had SCN4A mutations. Twenty-nine subjects from 18 kindreds had exon 22 and 24 mutations, confirming these exons to be hot spots. Unexpectedly, 3 of these subjects harbored mutations previously described with potassium-aggravated myotonia (G1306A, G1306E). We identified two new mutations (R1448L and L1436P). Ten cases (8 kindreds) without mutations exhibited paramyotonia congenita with prominent pain and weakness.

CONCLUSIONS

This study identifies two new mutations, confirms SCN4A as a common cause of paramyotonia congenita in the UK, and suggests further allelic and possibly genetic heterogeneity.

摘要

目的

研究一大群英国先天性钠通道性肌无力患者的临床和遗传特征。

方法

我们对英国范围内表现出先天性肌无力表型的患者进行了临床和分子遗传学研究。

结果

我们鉴定出42名受累个体（28个家族）。所有病例均符合我们对先天性肌无力临床诊断的核心标准。75%的患者（32例患者/20个家族）存在SCN4A突变。来自18个家族的29名受试者有外显子22和24突变，证实这些外显子为热点区域。出乎意料的是，其中3名受试者携带先前描述的与钾加重性肌强直相关的突变（G1306A、G1306E）。我们鉴定出两个新突变（R1448L和L1436P）。10例（8个家族）无突变的病例表现为伴有明显疼痛和肌无力的先天性肌无力。