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

具有近端支配性（HMSN-P）的遗传性运动神经病是一种常染色体显性疾病，我们首先在日本冲绳的患者中描述的是一种常染色体疾病。 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 therapy 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.家族的基因分析系统已在RDO Molecular Biology Lab中建立，该实验室是Sao Paulo University的合作设施。我于2011年8月5日在大学举行了有关HMSN-P的教育演讲。我们在美国密尔沃基市威斯康星州医学院的米歇尔·柯林斯（Michel Collins）与米歇尔·柯林斯（Michel Collins）合作研究了一个与德国血统的大家庭。在F…更友善的情况下，至少有4代患者表明常染色体显性遗传。它们具有HMSN-P的一些相似临床方面，并已被诊断为charcot-marie-tooth病或弗里德里希共济失调。我们对它们进行了详细的神经学检查，并从三名知情同意的患者那里获得了唾液以获得DNA。在韩国，我们有一些信息，表明HMSN-P喜欢症状的患者在韩国。然而，尚未进行详细的神经研究。他们认为，基于脑干和脊髓运动神经元与Optineurin涉及的神经病理学发现，HMSN-P可以被视为具有感官参与的伪造形式，这是一种新的认真基因。 HMSN-P的临床病理特征与SOD1突变的伪造相似。从上述研究中，人们可能会对该实体的分类为HMSN产生一些怀疑。虽然提出可能更好地将其视为具有感觉神经疾病的伪造，但HMSN-P的命名法实际上可能属于一个新的子类，这是在Als.t.t的肿瘤学上，HMSN-P的患者可能会在全球范围内存在于全球范围内携带fals的诊断，以使成人SMA或Charcot Marie Type type typer hand pathsmangy的诊断。神经疾病，例如伪造和SMA。较少的