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Abstract：
Mutations of the voltage-gated sodium channel gene (SCN4A), which encodes Nav1.4, cause nondystrophic myotonia that occasionally is associated with severe apnea and laryngospasm. There are case reports of nondystrophic myotonia due to mutations in the C-terminal tail (CTerm) of Nav1.4, but the functional analysis is scarce.
We present two families with nondystrophic myotonia harboring a novel heterozygous mutation (E1702del) and a known heterozygous mutation (E1702K).
The proband with E1702K exhibited repeated rhabdomyolysis, and the daughter showed laryngospasm and cyanosis. Functional analysis of the two mutations as well as another known heterozygous mutation (T1700_E1703del), all located on EF hand-like motif in CTerm, was conducted with whole-cell recording of heterologously expressed channel. All mutations displayed impaired fast inactivation.
The CTerm of Nav1.4 is vital for regulating fast inactivation. The study highlights the importance of accumulating pathological mutations of Nav1.4 and their functional analysis data.
We present two families with nondystrophic myotonia harboring a novel heterozygous mutation (E1702del) and a known heterozygous mutation (E1702K).
The proband with E1702K exhibited repeated rhabdomyolysis, and the daughter showed laryngospasm and cyanosis. Functional analysis of the two mutations as well as another known heterozygous mutation (T1700_E1703del), all located on EF hand-like motif in CTerm, was conducted with whole-cell recording of heterologously expressed channel. All mutations displayed impaired fast inactivation.
The CTerm of Nav1.4 is vital for regulating fast inactivation. The study highlights the importance of accumulating pathological mutations of Nav1.4 and their functional analysis data.
摘要：
电压门控钠通道基因（SCN4A）的突变，编码Nav1.4，引起非营养不良性肌强直，偶尔与严重的呼吸暂停和喉痉挛有关。由于Nav1.4的C末端尾部（CTerm）突变，有非营养不良性肌强直的病例报告，但功能分析很少。
我们提出了两个非营养不良性肌强直家族，它们有一个新的杂合突变（E1702del）和一个已知的杂合突变（E1702K）。
E1702K的先证者表现出反复的横纹肌溶解，女儿出现了喉痉挛和紫癜。对两种突变以及另一种已知的杂合突变（T1700_E1703del）进行功能分析，全部位于CTerm的EF手形图案上，进行异源表达通道的全细胞记录。所有突变均显示受损的快速失活。
Nav1.4的CTerm对于调节快速失活至关重要。该研究强调了积累Nav1.4的病理突变及其功能分析数据的重要性。
我们提出了两个非营养不良性肌强直家族，它们有一个新的杂合突变（E1702del）和一个已知的杂合突变（E1702K）。
E1702K的先证者表现出反复的横纹肌溶解，女儿出现了喉痉挛和紫癜。对两种突变以及另一种已知的杂合突变（T1700_E1703del）进行功能分析，全部位于CTerm的EF手形图案上，进行异源表达通道的全细胞记录。所有突变均显示受损的快速失活。
Nav1.4的CTerm对于调节快速失活至关重要。该研究强调了积累Nav1.4的病理突变及其功能分析数据的重要性。
