A novel mutation in CLCN1 associated with feline myotonia congenita.
A novel mutation in CLCN1 associated with feline myotonia congenita.
复制标题
DOI：
10.1371/journal.pone.0109926
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lyons LA
中科院分区：
文献类型：
--
作者：
Gandolfi B;Daniel RJ;O'Brien DP;Guo LT;Youngs MD;Leach SB;Jones BR;Shelton GD;Lyons LA
先天性肌强直（MC）是一种骨骼肌通道病，其特征是肌肉在随意收缩后不能放松。全世界人类的流行率为1∶ 100，000。在小鼠、狗、人和山羊中的研究证实了肌强直与氯离子通道的功能缺陷和骨骼肌氯离子通道（CLCN 1）的突变相关。CLCN 1编码骨骼肌细胞膜中最丰富的氯离子通道。对来自加拿大温尼伯的5只随机繁殖的MC猫进行了检查。所有猫都有突出的舌头，下颌运动范围有限，并有突出的颈部和近端肢体肌肉组织。所有猫在眼睑反射测试时均出现眼睑痉挛和短步幅步态。肌电图显示肌强直放电的平均频率为300 Hz，类似于“蜜蜂群”的声音。肌肉组织病理学显示所有纤维类型的肥大。CLCN 1的直接测序显示，只有受影响的猫的突变破坏了外显子16下游的供体剪接位点。突变蛋白的体外翻译预测了过早截短和部分缺乏对离子转运活性至关重要的高度保守的CBS 1（胱硫醚β-合酶）结构域和一个在通道形成中关键的二聚化结构域。对猫的来源地的温尼伯随机繁殖种群进行遗传筛查，确定了突变携带者。一种用于种群筛查的基因测试现在已经可以使用，并且可以从野生种群中识别携带者猫。
Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1∶100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a ‘swarm of bees’. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine β-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.
登录
查看更多内容
DOI：
10.1085/jgp.20028741
发表时间：
2003-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Duffield M;Rychkov G;Bretag A;Roberts M
通讯作者：
Roberts M
影响因子：
64.5
作者：
AEBI, M;HORNIG, H;WEISSMANN, C
通讯作者：
WEISSMANN, C
影响因子：
11.2
作者：
Fournier, Emmanuel;Viala, Karine;Fontaine, Bertrand
通讯作者：
Fontaine, Bertrand
影响因子：
30.8
作者：
GEORGE, AL;CRACKOWER, MA;EBERS, GC
通讯作者：
EBERS, GC
影响因子：
9.9
作者：
AMINOFF, MJ;LAYZER, RB;FADEN, AI
通讯作者：
FADEN, AI