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

遗传性近端显性运动感觉神经病(HMSN-P)是一种常染色体显性遗传性慢进性神经肌肉疾病，我们首先在日本冲绳的患者中进行了描述。HMSN-P基因座已被定位于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。我们与圣保罗大学的Paulo Euripedes Marchiori教授和Maria Teresa Alves Hirata博士合作，研究了两个具有日本血统的巴西日裔家庭的10名患者。这些家庭的基因分析系统已经在圣保罗大学的合作设施RDO分子生物学实验室建立。2011年8月5日，我在该大学做了一次关于HMSN-P的教育讲座。我们与美国密尔沃基威斯康星医学院神经科的Michel Collins博士合作，研究了一个具有德国血统的大家庭。在f…中更可喜的是，在4代中至少有10名患者提示常染色体显性遗传。他们有一些类似的HMSN-P的临床特征，并已被诊断为夏科-玛丽-图斯病或Friedreich共济失调。我们对他们进行了详细的神经学检查，并从三名知情同意获得DNA的患者那里获得了唾液。在韩国，我们有一些信息表明，韩国有HMSN-P样症状的患者。然而，还没有进行详细的神经学研究。Fujita K等人报告了一例HMSN-P尸检病例。根据脑干和脊髓运动神经元受累的神经病理学结果，他们提出HMSN-P可以被认为是一种感觉受累的FALS，而optineurin是FALS的一个新的致病基因。HMSN-P的临床病理特征与SOD1突变的FALS相似。从前面的研究中，人们可能会对这个实体被归类为HMSN提出一些疑问。HMSN-P的命名实际上可能属于ALS的一个新的亚类。可以想象，HMSN-P患者可能存在于世界各地，诊断为FALS、成人起病的SMA或Charcot-Marie-Tooth病2型。对HMSN-P确切发病机制的探索可能有助于阐明其他神经系统疾病，如FALS和SMA。较少

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