Clinical & Molecular Analysis of Neuromuscular Disorders

临床

• 批准号: 6334200
• 负责人: VIRGINIA Eunice KIMONIS
• 金额: $ 12.08万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-25 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6334200
• 关键词: Alzheimer's disease; clinical research; deafness; developmental genetics; embryogenesis; family genetics; gene expression; gene mutation; hereditary motor and sensory neuropathy; histogenesis; human subject; immunocytochemistry; in situ hybridization; laboratory mouse; labyrinth; linkage mapping; method development; microarray technology; molecular pathology; muscular dystrophy; neuromuscular disorder; osteitis deformans; phenotype; single strand conformation polymorphism; tissue /cell culture

DESCRIPTION (provided by applicant): Since the mid1980s, science has made tremendous progress in understanding genetics, including the roles that genes play in certain diseases. In particular, significant strides have been made towards identifying the molecular basis of neuromuscular disorders. These recent findings have initiated exciting studies of genebased therapies. The focus of our laboratory has been on the clinical and molecular pathogenesis of unique neuromuscular diseases of families from Central Illinois. The original K02 grant was for clinical and molecular delineation of a unique combination of features in a large family with CharcotMarieTooth and deafness. This ongoing study has led to the identification of a unique mutation in the PMP22 gene that cosegregates with the disease phenotype. We have recruited additional families to improve our understanding of this interesting phenotype. Molecular studies propose to examine the mechanism of hearing loss by determining patterns of PMP22 expression in the cochlea of mice throughout development and identifying new PMP22 mutations associated with deafness. As a result of our interest in neuromuscular disorders we have expanded our research interests to include another unique disorder: autosomal dominant limbgirdle muscular dystrophy in combination with Paget disease of bone and Alzheimer disease in some individuals. We have mapped this disorder to a unique focus on chromosome 9. The focus of our research is to identify the gene that disrupts basic cell function and causes a myriad of phenotypes in this family. The aim of the current grant is to develop molecular and analytical techniques that will advance our understanding of CharcotMarieTooth disease, limbgirdle muscular dystrophy and other neuromuscular disorders. The suggested training will provide the PI with skills necessary to investigate the clinical and basic molecular pathogenesis of these disorders and aid in the development of novel treatment protocols.

描述（由申请人提供）：自20世纪80年代中期以来，科学已经使 在理解遗传学方面取得了巨大的进步，包括基因的作用， 在某些疾病中发挥作用。特别是， 以确定神经肌肉疾病的分子基础。这些 最近的发现引发了对基于基因的疗法的令人兴奋的研究。 我们实验室的重点一直是临床和分子发病机制 伊利诺伊州中部的家族中的独特神经肌肉疾病。的 最初的K02拨款是用于临床和分子描绘一种独特的 在一个大家族的特点与CharcotMarieTooth和耳聋的组合。 这项正在进行的研究已经导致在一个独特的突变的鉴定， 与疾病表型共分离的PMP22基因。我们招募了 更多的家庭，以提高我们对这个有趣的表型的理解。 分子研究建议通过以下方法来检查听力损失的机制： 确定小鼠耳蜗中PMP22表达的模式 开发和鉴定与耳聋相关的新的PMP22突变。 由于我们对神经肌肉疾病的兴趣，我们扩大了我们的 研究兴趣包括另一种独特的疾病：常染色体显性遗传 肢带型肌营养不良症合并佩吉特骨病， 阿尔茨海默病在某些人。我们将这种疾病定位为一种独特的 关注9号染色体我们研究的重点是找出 破坏了基本的细胞功能，并导致该家族中的无数表型。 目前赠款的目的是发展分子和分析技术 这将促进我们对CharcotMarieTooth疾病的理解， 肌肉萎缩症和其它神经肌肉疾病。建议的培训 将为PI提供必要的技能，以研究临床和基础 这些疾病的分子发病机制，并帮助开发新的 治疗方案。

项目成果

Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.

骨和肌肉营养不良的家族性显性佩吉特病的异质性。

• DOI: 10.1002/ajmg.10199
• 发表时间: 2002
• 期刊: American journal of medical genetics
• 作者: Waggoner,Brook;Kovach,MargaretJ;Winkelman,Marc;Cai,Dan;Khardori,Romesh;Gelber,David;Kimonis,VirginiaE
• 通讯作者: Kimonis,VirginiaE