MOLECULAR-BASIS OF THOMSEN DISEASE (AUTOSOMAL DOMINANT MYOTONIA-CONGENITA)
MOLECULAR-BASIS OF THOMSEN DISEASE (AUTOSOMAL DOMINANT MYOTONIA-CONGENITA)
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DOI：
10.1038/ng0493-305
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发表时间：
1993-04-01
期刊：
影响因子：
30.8
通讯作者：
EBERS, GC
中科院分区：
文献类型：
--
作者：
GEORGE, AL;CRACKOWER, MA;EBERS, GC
汤姆森病（常染色体显性先天性肌强直）最近被发现与人类骨骼肌氯通道基因（HUMCLC）区域的染色体7q35有关。单链构象多态性分析（SSCP）用于筛选来自4个不相关家系的成员的DNA，以寻找HUMCLC突变。在所有受影响的人中都检测到异常带，但在三个家庭中没有未受影响的个体。直接测序揭示了G到a的转变，导致谷氨酸取代了位于第三和第四个预测膜跨越段之间的甘氨酸残基。甘氨酸残基在所有已知的这类氯离子通道蛋白中都是保守的。这些发现确立了HUMCLC是汤姆森氏病基因。
Thomsen's disease (autosomal dominant myotonia congenita) has recently been linked to chromosome 7q35 in the region of the human skeletal muscle chloride channel gene (HUMCLC). Single strand conformation polymorphism analysis (SSCP) was used to screen DNA from members of four unrelated pedigrees with this disorder for mutations in HUMCLC. Abnormal bands were detected in all affected, but no unaffected individuals in three of the families. Direct sequencing revealed a G to A transition that results in the substitution of a glutamic acid for a glycine residue located between the third and fourth predicted membrane spanning segments. This glycine residue is conserved in all known members of this class of chloride channel proteins. These findings establish HUMCLC as the Thomsen's disease gene.