Identification of novel mutations of the CLCN1 gene for myotonia congenital in China.
OBJECTIVE
The identification of disease-specific genetic and electrophysiological patterns for myotonia congenital (MC) could help clinicians apply in the findings of genetic studies to improve diagnosis. We examined the molecular, clinical, and histopathological characteristics of eight patients with MC.


METHODS
Optimization PCR was used to exclude myotonic dystrophies and the CLCN1 gene was sequenced in patients having clinical and electrophysiological features indicative of MC.


RESULTS
Genetic screening identified nine CLCN1 mutations among the eight patients, including two missense, three nonsense, two insertion, and two deletion mutations. The patients showed typical myotonia and muscle hypertrophy. In contrast to the previous studies, secondary dystonia, joint contracture, and abnormal cardiac activity were also observed. Patients with novel mutations did not show any new muscle pathology compared with established mutations. Disscussion: Molecular genetics analysis offers an accurate method for diagnosing MC. The results of this analysis should be considered alongside clinical and electrophysiological characteristics. In this study, novel mutations in CLCN1 were detected, and the spectrum of CLCN1 mutations known to be associated with MC was expanded.
a Department of Neuromuscular Disorders , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Yan-Xin
YX
Meng
a Department of Neuromuscular Disorders , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Zhe
Z
Zhao
a Department of Neuromuscular Disorders , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Hong-Rui
HR
Shen
a Department of Neuromuscular Disorders , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Qi
Q
Bing
a Department of Neuromuscular Disorders , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Jing
J
Hu
D002648:Child; D002681:China; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004576:Electromyography; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics* / Q000473:pathology; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics; D012720:Severity of Illness Index
C086321:CLC-1 channel; D018118:Chloride Channels; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human
CLCN1; Myotonia congenita; Non-dystrophic myotonias; Novel mutations; SCN4A