Novel chloride channel mutations leading to mild myotonia among Chinese.
We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.
Burgunder
Jean-Marc
JM
Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. jm.burgunder@dkf6.unibe.ch
Huifang
Shang
S
Beguin
Pascal
P
Baur
Roland
R
Eng
Chew Soh
CS
Seet
Raymond C S
RC
Lim
Erle C H
EC
Ong
Benjamin K C
BK
Hunziker
Walter
W
Sigel
Erwin
E
D000293:Adolescent; D000818:Animals; D002681:China; D018118:Chloride Channels / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004576:Electromyography; D004594:Electrophysiology; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009222:Myotonia / Q000235:genetics* / Q000473:pathology; D009460:Neurologic Examination; D009865:Oocytes / Q000378:metabolism; D010146:Pain / Q000209:etiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014981:Xenopus
C086321:CLC-1 channel; D018118:Chloride Channels; D018076:DNA, Complementary