Inherited Neurophathies Consortium (RDCRC)

描述（由申请方提供）：Charcot玛丽牙病（CMT）是遗传性周围神经病变的代名词。这些是最常见的遗传性神经肌肉疾病之一，大约每2500人中就有1人受到影响。超过30个基因的突变导致CMT，并且已经确定了超过40个额外基因的位点。CMT可分为三个特定的组：（1）CMT 1，显性遗传性脱髓鞘神经病;（2）CMT 2，显性遗传性轴突神经病;和（3）CMT 4，隐性遗传性神经病。对于许多形式的CMT，存在遗传上真实的动物模型，并且已经提供了迫使目前正在进行的针对CMT 1A的人体临床试验的数据。尽管取得了这些进展，但对于任何形式的CMT都没有有效的治疗方法，只有最常见的类型（CMT 1A和CMT 1X）的自然史数据可用，许多潜在的基因型-表型相关性仍然未知。为了解决这些问题，我们创建了遗传性神经病联盟（HNC），这是一个在CMT方面具有专业知识的临床研究人员的集合。HNC内的研究中心包括韦恩州立大学、伦敦的国立神经病学/神经外科医院、罗切斯特大学/肌肉研究小组（MSG）、宾夕法尼亚大学/费城儿童医院（CHOP）和佛罗里达的迈阿密大学。将开展两个试点项目。来自WSU的Gyula Acsadi博士将在来自伦敦的Muntoni博士和来自CHOP的Finkel博士的帮助下为CMT患者开发一个儿科评分系统。谢勒博士将为对CMT感兴趣的患者和研究人员开发一个以OMIM为模式的网站。将开展两项临床研究项目。来自WSU的Shy博士将对CMT 1B、CMT 2A和CMT 4A进行自然历史分析。来自迈阿密的Zuchner博士和万斯博士将在各种形式的CMT中寻找修饰基因。来自伦敦的玛丽赖利博士将领导一个针对博士后研究员和初级教员的培训项目，该项目将涉及包括MSG在内的所有网站。来自罗切斯特的McDermott博士将担任HNC生物统计学家。Charcot玛丽牙协会、CMT联合王国和联合国国家导弹防御系统组织将与国家委员会进行广泛的互动。公共卫生相关性：这些项目将提供深入了解疾病机制，开发治疗方法，并教育未来的遗传性神经病研究人员。

DESCRIPTION (provided by applicant): Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. These are among the most common inherited neuromuscular diseases, affecting approximately 1 in 2500 people. Mutations in more than 30 genes cause CMT, and loci for more than 40 additional genes have been identified. CMT is separable into three specific groups: (1) CMT1, dominantly inherited demyelinating neuropathies; (2) CMT2, dominantly inherited axonal neuropathies; and (3) CMT4, recessively inherited neuropathies. Genetically authentic animal models exist for many forms of CMT, and have provided the data compelling the clinical trials in humans that are currently underway for CMT1 A. Despite these advances, no effective therapies are available for any form of CMT, natural history data are available for only the most common types (CMT1A and CMT1X), and many potential genotype-phenotype correlations remain unknown. To address these issues, we have created the Hereditary Neuropathy Consortium (HNC), a collection of clinical researchers with demonstrated expertise in CMT. Sites within the HNC include Wayne State University, the National Hospital for Neurology/Neurosurgery in London, the University of Rochester/Muscle Study Group (MSG), the University of Pennsylvania/Children's Hospital of Philadelphia (CHOP), and the University of Miami, Florida. Two Pilot Projects will be performed. Dr. Gyula Acsadi from WSU will develop a Pediatric Scoring System for CMT patients, aided by Dr. Muntoni from London and Dr. Finkel from CHOP. Dr. Scherer will develop a Website patterned after OMIM for patients and researchers interested in CMT. Two Clinical Research Projects will be performed. Dr. Shy, from WSU, will undertake a natural history analysis of CMT1B, CMT2A, and CMT4A. Drs Zuchner and Vance, from Miami, will perform a search for modifier genes in various forms of CMT. Dr. Mary Reilly from London will lead a training program for postdoctoral fellows and junior faculty members that will involve all sites including the MSG. Dr. McDermott, from Rochester, will be the HNC Biostatistician. The Charcot Marie Tooth Association (CMTA), CMT United Kingdom (CMTUK) and TREAT-NMD organizations will interact extensively with the HNC. PUBLIC HEALTH RELEVANCE: These projects will provide insights into disease mechanisms develop therapies and educate future investigators for the inherited neuropathies.