Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
Department of Neurology, Wakayama Medical University, Kimiidera, Wakayama, Wakayama, Japan.
Muscle Nerve. 2020 Jun;61(6):808-814. doi: 10.1002/mus.26849. Epub 2020 Mar 17.
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.
电压门控钠离子通道基因（SCN4A）的突变，其编码Nav1.4，导致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。有报道称，Nav1.4 的 C 末端尾部（CTerm）突变会导致非营养不良性肌强直，但功能分析却很少。
我们介绍了两个家族的非营养不良性肌强直，均携带一个新的杂合突变（E1702del）和一个已知的杂合突变（E1702K）。
携带 E1702K 的先证者表现为反复横纹肌溶解，其女儿表现为喉痉挛和发绀。对位于 CTerm 的 EF 手样模体上的两个突变（E1702K 和 T1700_E1703del）以及另一个已知的杂合突变（T1700_E1703del）进行了异源表达通道的全细胞记录，进行了功能分析。所有突变均显示快速失活受损。
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 的病理性突变及其功能分析数据的重要性。
