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EF hand‐like motif mutations of Nav1.4 C‐terminus cause myotonic syndrome by impairing fast inactivation
Author(s) -
Horie Riho,
Kubota Tomoya,
Koh Jinsoo,
Tanaka Rieko,
Nakamura Yuichiro,
Sasaki Ryogen,
Ito Hidefumi,
Takahashi Masanori P.
Publication year - 2020
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26849
Subject(s) - myotonia , missense mutation , genetics , sodium channel , mutation , proband , exon , microbiology and biotechnology , biology , chemistry , gene , myotonic dystrophy , organic chemistry , sodium
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. Methods We present two families with nondystrophic myotonia harboring a novel heterozygous mutation (E1702del) and a known heterozygous mutation (E1702K). Results 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. Discussion 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.