Abstract：
BACKGROUND: This study aimed to characterize the genetic, pathological, and clinical alterations of 17 patients in China presenting with nondystrophic myotonia (NDM) and to analyze the relationship between genotype and clinical phenotype.
METHODS: CLCN1 and SCN4A genes in patients with clinical features and muscle pathology indicative of NDM were sequenced. Furthermore, KCNE3 and CACNA1S genes were assessed in patients with wild-type CLCN1 and SCN4A.
RESULTS: Patients may have accompanying atypical myopathy as well as muscle hypertrophy, secondary dystonia, and joint contracture as determined by needle electromyography. All the study participants were administered mexiletine in combination with carbamazepine and showed significant improvements in myotonia symptoms in response to this therapy. CLCN1 gene mutation was detected in 8 cases diagnosed with myotonia congenital using gene screening. The detected mutations included 5 missense, 2 nonsense, 1 deletion, and 2 insertions. Further gene analysis showed 4 mutations in the SCN4A gene in patients diagnosed with paramyotonia congenita.
CONCLUSIONS: Myotonia congenita and paramyotonia congenita are the predominant forms of NDM in China. NDM may be best diagnosed using genetic analysis in associated with clinical features.
METHODS: CLCN1 and SCN4A genes in patients with clinical features and muscle pathology indicative of NDM were sequenced. Furthermore, KCNE3 and CACNA1S genes were assessed in patients with wild-type CLCN1 and SCN4A.
RESULTS: Patients may have accompanying atypical myopathy as well as muscle hypertrophy, secondary dystonia, and joint contracture as determined by needle electromyography. All the study participants were administered mexiletine in combination with carbamazepine and showed significant improvements in myotonia symptoms in response to this therapy. CLCN1 gene mutation was detected in 8 cases diagnosed with myotonia congenital using gene screening. The detected mutations included 5 missense, 2 nonsense, 1 deletion, and 2 insertions. Further gene analysis showed 4 mutations in the SCN4A gene in patients diagnosed with paramyotonia congenita.
CONCLUSIONS: Myotonia congenita and paramyotonia congenita are the predominant forms of NDM in China. NDM may be best diagnosed using genetic analysis in associated with clinical features.
摘要：
背景：这项研究旨在表征遗传，病态,分析17例非营养不良性肌强直（NDM）患者的临床改变，并分析基因型与临床表型之间的关系。
方法：对具有NDM临床特征和肌肉病理指示的患者CLCN1和SCN4A基因进行测序。此外，在患有野生型CLCN1和SCN4A的患者中评估KCNE3和CACNA1S基因。
结果：患者可能伴有不典型肌病和肌肉肥大，继发性肌张力障碍,和通过针肌电图确定的关节挛缩。所有研究参与者都接受了美西律与卡马西平的联合治疗，并显示出对该疗法的肌强直症状的显着改善。对8例先天性肌强直患者进行基因筛查,检测CLCN1基因突变。检测到的突变包括5个错义，2废话，1个删除,2插入。进一步的基因分析显示，在诊断为先天性副肌强直的患者中，SCN4A基因有4个突变。
结论：先天性肌强直和先天性副肌强直是我国NDM的主要形式。使用与临床特征相关的遗传分析可以最好地诊断NDM。
方法：对具有NDM临床特征和肌肉病理指示的患者CLCN1和SCN4A基因进行测序。此外，在患有野生型CLCN1和SCN4A的患者中评估KCNE3和CACNA1S基因。
结果：患者可能伴有不典型肌病和肌肉肥大，继发性肌张力障碍,和通过针肌电图确定的关节挛缩。所有研究参与者都接受了美西律与卡马西平的联合治疗，并显示出对该疗法的肌强直症状的显着改善。对8例先天性肌强直患者进行基因筛查,检测CLCN1基因突变。检测到的突变包括5个错义，2废话，1个删除,2插入。进一步的基因分析显示，在诊断为先天性副肌强直的患者中，SCN4A基因有4个突变。
结论：先天性肌强直和先天性副肌强直是我国NDM的主要形式。使用与临床特征相关的遗传分析可以最好地诊断NDM。
