Kuo H-C, Hsiao K-M, Chang L-I, You T-H, Yeh T-H, Huang C-C
Department of Neurology, Chang Gung Memorial Hospital and University, Taipei, Taiwan.
Acta Neurol Scand. 2006 May;113(5):342-6. doi: 10.1111/j.1600-0404.2006.00589.x.
Myotonia congenita (MC), caused by mutations in the muscle chloride channel (CLCN1) gene, can be inherited dominantly or recessively. The mutations at the carboxyl terminus of the CLCN1 gene have been identified in MC patients, but the functional implication of these mutations is unknown.
Direct sequencing of polymerase chain reaction products covering the whole coding region of the CLCN1 gene was performed in a MC family. This study was designed to investigate the clinical manifestations and genetic analysis of the CLCN1 gene.
We identified two novel mutations, 2330delG and 1892C>T, from a genetic screening of the CLCN1 gene in the MC family. The 2330delG mutant allele producing a fs793X truncated protein was identified in a heterozygous state in all the patients. The 1892C>T nucleotide change induced a missense mutation (T631I) found in several asymptomatic individuals, indicating that it may not be associated with MC. Intriguingly, the 2330delG mutation was also found in an asymptomatic subject who also carried the 1892C>T mutation.
The data indicate that the fs793X mutant protein causes dominantly inherited MC. Because the mutation has been found in a recessive pedigree, the fs793X mutation may have a dual inheritance pattern.
先天性肌强直（MC）由肌肉氯离子通道（CLCN1）基因突变引起，可呈显性或隐性遗传。已在MC患者中鉴定出CLCN1基因羧基末端的突变，但这些突变的功能意义尚不清楚。
对一个MC家系进行了覆盖CLCN1基因整个编码区的聚合酶链反应产物的直接测序。本研究旨在调查CLCN1基因的临床表现和基因分析。
我们在该MC家系的CLCN1基因遗传筛查中鉴定出两个新突变，即2330delG和1892C>T。在所有患者中均鉴定出产生fs793X截短蛋白的2330delG突变等位基因，呈杂合状态。1892C>T核苷酸变化导致在几个无症状个体中发现错义突变（T631I），表明它可能与MC无关。有趣的是，在一名也携带1892C>T突变的无症状个体中也发现了2330delG突变。
数据表明fs793X突变蛋白导致显性遗传的MC。由于该突变已在一个隐性系谱中发现，fs793X突变可能具有双重遗传模式。
