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

遗传性运动感觉神经病伴近端优势（HMSN-P）是一种常染色体显性遗传的缓慢进行性神经肌肉疾病，我们首先在日本冲绳的患者中描述。HMSN-P基因定位于3号染色体上的一个重叠着丝粒区域。本研究的目的是阐明HMSN-P的全球流行病学、发病机制和治疗策略。圣保罗大学合作的RDO分子生物学实验室建立了家系的基因分析系统。我于2011年8月5日在<th>美国密尔沃基的威斯康星州医学院神经病学系与Michel柯林斯博士合作，对一个具有德国血统的大家庭进行了研究。在f 关于我们 家族4代至少有10例为常染色体显性遗传。他们有一些类似的HMSN-P的临床方面，并已被诊断为夏科-玛丽-图思病或弗里德赖希共济失调。我们对他们进行了详细的神经学检查，并在知情同意的情况下从三名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患有HMSN-P样症状的患者在韩国。Fujita K等报道了一例HMSN-P的尸检病例，根据其脑干和脊髓运动神经元与新发现的FALS致病基因optineurin的关系，提出HMSN-P可能是一种感觉受累的FALS。HMSN-P的临床病理特征与SOD 1突变型FALS相似。从上述研究中，人们可能会对这种实体作为HMSN的分类产生一些疑问。HMSN-P的命名可能属于ALS疾病分类学下的一个新的亚类。可以想象，HMSN-P患者可能在世界范围内存在着被诊断为ALS、成人发作的SMA或Charcot-Marie-Tooth病2型的患者。对HMSN-P确切病理机制的探索可能有助于阐明其他神经系统疾病，例如FALS和SMA。少

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