Genetic bases for Charcot-Marie-Tooth and Hereditary Sensory type 1 Neuropathies

该项目旨在鉴定一种遗传性周围神经疾病中的缺陷基因。周围神经遗传性疾病是人类最常见的遗传性疾病，统称为Charcot-Marie-Tooth神经病。虽然很少有遗传性神经疾病是致命的，但大多数会导致终生残疾。所有这些都会导致小腿无力，然后导致手臂和手的肌肉无力和消瘦。受影响的人跑步困难，经常摔倒，残疾逐渐增加，最终需要夹板和其他助行器。我们建议利用人类基因组计划最新开发的资源来定位缺陷基因。在以前的研究中，我们已经使用这些方法定位了另外两种遗传性神经疾病的缺陷基因。在这项研究中，我们建议研究一种新认识的CMT形式，称为中间CMT。中间CMT的特征介于影响神经本身(轴突)或神经绝缘(周围的髓鞘)的较知名形式的CMT之间。因此，这种疾病可能会影响到神经的两个组成部分。受影响的基因可能调节神经和其鞘之间的通讯。这项研究将对维持正常神经的机制提供有价值的见解。因此，发现该基因可能与许多其他神经疾病有关。这项研究是一项系统的研究，应该会找到导致这种疾病的异常基因。一旦知道了涉及的基因，就会开发出一种有效的测试方法。当我们可以对这种疾病进行测试时，我们可能会发现这种疾病比之前认识到的要常见得多。了解这种基因的功能将有助于了解疾病是如何发展的，并最终将导致有效的治疗。

This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradually increasing disability eventually requiring splints and other walking aids. We propose to use the newly developed resources of the human genome project to locate the defective gene. In previous studies we have used these methods to locate the defective genes of 2 other hereditary diseases of nerve. In this study we propose to investigate a newly recognised form of CMT called intermediate CMT. Intermediate CMT has characteristics intermediate between the better known forms of CMT affecting the nerve itself (the axon) or the nerve insulation (the surrounding myelin sheath). The disorder may therefore affect both components of nerve. The affected gene may mediate communication between the nerve and its sheath. This research should give valuable insight into the mechanisms responsible for the maintenance of normal nerve. Finding the gene may therefore have relevance to many other diseases of nerve. This research is a systematic search and should lead to the abnormal gene causing the disease. Once the gene involved is known then an effective test will be developed. When we can test for the disease, we probably will find that the disorder is much more common than previously recognised. Knowledge of the function of this gene will lead to an understanding of how the disease develops and will eventually lead to effective treatments.