Hoffman E P
Department of Molecular Genetics, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Annu Rev Med. 1995;46:431-41. doi: 10.1146/annurev.med.46.1.431.
The pathological genetic defects in the inherited myotonias and periodic paralyses were recently elucidated using molecular genetic studies. These disorders are usually transmitted as a dominant trait from an affected parent to a child. The many clinical symptoms include cold-induced uncontrollable contraction of muscle, potassium-induced contraction and paralysis, myotonia with dramatic muscular hypertrophy, muscle stiffness, and insulin-induced paralysis (in males). Horses afflicted with the disorder can suddenly collapse, despite an impressive physique. In the past three years, these clinically defined disorders have been shown to share a common etiology: subtle defects of ion channels in the muscle-fiber membrane. Although the specific ion channel involved varies depending on the disease, most patients have single amino acid changes in the channel proteins, with both normal and mutant channels present in each muscle fiber. For each patient, we can now establish a precise molecular diagnosis in the face of overlapping clinical symptoms and begin specific pharmacological treatment based on the primary problem. These studies have also provided insight into basic muscle biology and emphasize the careful regulation of ions in muscle excitation.
近期通过分子遗传学研究阐明了遗传性肌强直和周期性瘫痪中的病理遗传缺陷。这些疾病通常作为显性性状从患病父母传给子女。许多临床症状包括寒冷诱发的肌肉无法控制的收缩、钾诱发的收缩和瘫痪、伴有显著肌肉肥大的肌强直、肌肉僵硬以及胰岛素诱发的瘫痪（男性）。患这种疾病的马匹尽管体格健壮，却可能突然倒下。在过去三年中，这些临床定义的疾病已被证明有一个共同的病因：肌纤维膜中离子通道的细微缺陷。虽然所涉及的特定离子通道因疾病而异，但大多数患者的通道蛋白有单个氨基酸变化，每个肌纤维中同时存在正常和突变通道。对于每位患者，面对重叠的临床症状，我们现在可以进行精确的分子诊断，并根据主要问题开始进行特定的药物治疗。这些研究还为基础肌肉生物学提供了见解，并强调了肌肉兴奋中离子的精细调节。
