The overseas scientific research for the elucidation of the mechanism of a novel hereditary motor sensory neuropathy originated in Japan

起源于日本的新型遗传性运动感觉神经病发病机制的海外科学研究

基本信息

批准号：
21406026
负责人：
NAKAGAWA Masanori
金额：
$ 10.07万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

The hereditary motor sensory neuropathy with proximal dominancy(HMSN-P) is an autosomal dominant slowly progressive neuromuscular disease that we first described in patients from Okinawa, Japan. The gene locus of HMSN-P has been mapped to an overlapping centromeric region on chromosome 3.The purpose of this research is to clarify the global epidemiology, pathomechanism and therapeutic strategy for HMSN-P.We studied 10 patients in two Japanese Brazilian families with Japanese ancestry in collaboration with Prof. Paulo Euripedes Marchiori and Dr. Maria Teresa Alves Hirata in Sao Paulo University. The gene analysis system of the families has been established in RDO Molecular biology lab that is a collaboration facility of Sao Paulo University. I gave an educational lecture on HMSN-P at Aug. 5^<th>, 2011 in the University.We studied a large family with German ancestry in collaboration with Dr. Michel Collins in Department of Neurology, Medical College of Wisconsin, Milwaukee, USA. In the f … More amily, there are at least 10 patients in 4 generations suggesting autosomal dominant inheritance. They have some similar clinical aspects of HMSN-P and have been diagnosed as Charcot-Marie-Tooth disease or Friedreich ataxia. We examined them neurologically in detail and obtained the saliva from three patients with informed consent to obtain DNA.In Korea, we have some information suggesting that patients with HMSN-P like symptoms are in Korea. No detail neurological study, however, has been done.Fujita K et al reported an autopsy case of HMSN-P. They proposed that HMSN-P could be considered as a form of FALS with sensory involvement, based on the neuropathological findings of brainstem and spinal cord motor neuron involvement with optineurin, which is a new causative gene of FALS. The clinicopathological features of HMSN-P are similar to those of SOD1 mutated FALS. From the foregoing studies, one may cast some doubt on the classification of this entity as HMSN. While proposed that it might be better regarded as FALS with sensory neuronopathy, the nomenclature of HMSN-P may actually belong to a new subclass under the nosology of ALS.It is conceivable that patients with HMSN-P may exist worldwide carrying a diagnosis of FALS, adult onset SMA or Charcot-Marie-Tooth disease type 2.The quest for the exact pathomechanism of HMSN-P may contribute to clarification of other neurological diseases, such as FALS and SMA. Less

具有近端Domincy（HMSN-P）的遗传性感觉是一种常染色体显性疾病，缓慢地编程了我们在日本冲绳的患者中所描述的。 HMSN-P的全球流行病学，病理学和治疗策略。我们在日本的日本家庭与日本的家庭与Paulo Euripedes Marchiori教授和玛丽亚·特雷莎·阿拉塔（Maria Teresa Alata）教授在圣保罗大学的基因分析系统中。我在2011年在Milwaukee的Onsin，在2011年8月5日就对HMSN-P进行了教育。建议常染色体显性遗传。是。跌倒的基因。对于一个新的子类，在ALS的肿瘤学下，可以想象，全世界的患者携带了伪造的诊断。 SMA