Phenotypic variability of autosomal dominant myotonia congenita in a Taiwanese family with muscle chloride channel (CLCN1) mutation.
BACKGROUND
Myotonia congenita (MC), whether inherited in autosomal dominant or recessive form, is caused by mutation of CLCN1 on chromosome 7 and associated with impaired skeletal muscle relaxation after contraction. The basic pathophysiology is the reduction of chloride conductance in skeletal muscles caused by various molecular mechanisms. The cause of the wide phenotypic variability in both dominant and recessive MC remains unclear.


METHODS
A family clinically diagnosed with autosomal dominant myotonia congenita was enrolled. Three family members underwent a detailed neurological examination, eletromyography, and genetic analysis.


RESULTS
A G230E mutation of CLCN1 was confirmed in these three family members. One of them was completely asymptomatic and the electromyographic studies were normal. A great variability of clinical presentation was found in these family members with MC.


CONCLUSIONS
We report the first autosomal dominant MC family with G230E mutation in oriental countries. Most of the previously reported MC families with G230E mutation were autosomal dominant pedigrees, and only 1 out of 20 heterozygous family members was asymptomatic. The reduced penetrance in this family indicates a less "dominant negative effect" of the G230E mutation.
Chang
Ting-Yu
TY
Department of Neurology, Chang Gung Memorial Hospital and University, Taipei, Taiwan.
Kuo
Hung-Chou
HC
Hsiao
Kuang-Ming
KM
Huang
Chin-Chang
CC
D000293:Adolescent; D000368:Aged; D018118:Chloride Channels / Q000235:genetics*; D004576:Electromyography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009224:Myotonia Congenita / Q000235:genetics* / Q000628:therapy; D010641:Phenotype
C086321:CLC-1 channel; D018118:Chloride Channels