Fourth International MHE Research Conference

摘要：多发性遗传性外生骨病（Multiple Hereditary Exostoses， MHE）是一种常染色体显性遗传病，发病率约为五万分之一。MHE（也称为遗传性多发性外生骨瘤或多发性骨软骨瘤）的特征是称为外生骨瘤的软骨外生骨瘤生长在骨骼元素生长板附近，冲击周围组织并导致神经和肌腱受压，随之而来的疼痛和运动障碍；慢性疼痛;骨骼畸形;早发性骨关节炎。大约2%的患者会变成恶性肿瘤。目前的治疗是姑息性的，患者与疼痛和行动不便作斗争，一生中要经历多次手术。MHE是由负责硫酸肝素合成的EXT1和EXT2的功能缺失突变引起的，患者表现出不同程度的硫酸肝素缺乏。硫酸乙酰肝素链调节了大量关键的生理过程，解释了MHE患者一生中遭受的多种症状和健康问题。由于这种复杂性，对MHE的理解和寻找治疗方法需要多方面的方法，包括遗传学、酶学、糖生物学、发育生物学和矫形学，以及不同学科之间的思想交流和合作努力。因此，“第四届国际MHE研究会议”的主要目标是汇集研究MHE和照顾MHE患者的医生、医生科学家和科学家，以及在密切相关领域工作的其他科学家，包括骨骼发育和生长、人类遗传骨骼疾病、药物发现、人类疾病的哺乳动物和非哺乳动物动物模型。除了在各自领域处于研究前沿之外，受邀演讲者还具有不同的专业知识和观点。因此，会议将作为一个及时和有力的论坛，交流最新数据，将产生关于MHE发病机制的新想法、新方法和新假设，并将促进不同领域研究人员之间的进一步互动。会议将在宾夕法尼亚大学举行

DESCRIPTION (provided by applicant): Abstract Multiple Hereditary Exostoses (MHE) is an autosomal dominant disorder that affects about 1 in 50,000 children. MHE (also known as Hereditary Multiple Exostoses or Multiple Osteochondromas) is characterized by cartilaginous outgrowths called exostoses that develop adjacent to the growth plates of skeletal elements, impinge onto surrounding tissues and cause: compression of nerves and tendons with consequent pain and impairment of motion; chronic pain; skeletal deformities; and early onset osteoarthritis. They become malignant in about 2% of the patients. Current therapies are palliative, and patients struggle with pain and limited mobility and undergo multiple surgeries through life. MHE is caused by loss-of-function mutations in EXT1 and EXT2 that are responsible for heparan sulfate synthesis, and patients display varying degrees of heparan sulfate deficiency. Heparan sulfate chains regulate a significant number of critical physiologic processes, accounting for the multitude of symptoms and health problems from which MHE patients suffer throughout their life. Because of such complexity, the understanding of MHE and finding a cure require multifaceted approaches that involve genetics, enzymology, glycobiology, developmental biology, and orthopedics, and an exchange of ideas and the establishment of collaborative efforts among various disciplines. Hence, the key objective of the "Forth International MHE Research Conference" is to bring together physicians, physicians-scientists and scientists who study MHE and care for MHE patients and additional scientists who work in closely related fields, including skeletal development and growth, human genetic skeletal diseases, drug discovery, and mammalian and non-mammalian animal models of human diseases. In addition to being at the forefront of research in their fields, the invited speakers have diverse expertise and perspectives. Thus, the Conference will serve as a timely and vigorous forum for the exchange of the most recent data, will generate new ideas, approaches and hypotheses about the pathogenesis of MHE, and will promote further interactions amongst researchers in different fields. The Conference will be held at the In at Penn at the University of Pennsylvania in Philadelphia on November 1-4, 2012, will have eight sessions on MHE clinical manifestation and orthopaedics, human genetics, developmental biology, heparan sulfate chemistry, animal disease models and related bone diseases, and about 50 participants (including over 3o invited speakers and non-speaking discussants). Each session will have three to four speakers who will present 20-minute talks followed by 10 minutes of discussion. The format, roster, and size of the meeting are designed to maximize interactions among participants in an informal setting. Because of the encompassing roles of heparan sulfate in human physiology, the Conference will have broad and far-reaching impact and relevance for both basic research and translational and clinical medicine. As importantly, it will provide a renewed sense of hope to patients and families alike that MHE is being actively studied and a cure will one day be found. PUBLIC HEALTH RELEVANCE: Narrative Multiple hereditary exostoses is a debilitating genetic disorder characterized by the formation of multiple bony protrusions that cause a significant number of symptoms and pathological consequences This conference aims to promote the exchange of the most current information regarding MHE and the collaboration and synergy among laboratories studying this disease. This goal will be accomplished by bringing together world experts in the fields of orthopedics, human genetics, developmental biology, glycobiology, and related human bone diseases, and by providing them with a highly focused forum to cultivate new ideas, foster cross-discipline collaborations, discover the pathogenesis of the disease and begin to envision possible ways to treat it.