Fourth International MHE Research Conference

描述（申请人提供）：摘要多发性遗传性外生骨疣（MHE）是一种常染色体显性遗传疾病，影响约1/50，000的儿童。MHE（也称为遗传性多发性外生骨疣或多发性骨软骨瘤）的特征在于称为外生骨疣的软骨增生，其邻近骨骼元件的生长板发育，撞击周围组织并导致：神经和肌腱的压迫，随之而来的疼痛和运动障碍;慢性疼痛;骨骼畸形;和早发性骨关节炎。它们在大约2%的患者中变成恶性的。目前的疗法是姑息性的，患者在痛苦和行动不便中挣扎，一生中要接受多次手术。MHE是由负责硫酸乙酰肝素合成的EXT 1和EXT 2的功能缺失突变引起的，患者表现出不同程度的硫酸乙酰肝素缺乏症。硫酸乙酰肝素链调节大量的关键生理过程，导致MHE患者一生中遭受的众多症状和健康问题。由于这种复杂性，MHE的理解和找到治疗方法需要多方面的方法，涉及遗传学，酶学，糖生物学，发育生物学和整形外科学，以及交流思想和建立各学科之间的合作努力。因此，“第四届国际MHE研究会议”的主要目标是将研究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聚集在一起，包括骨骼发育和生长，人类遗传骨骼疾病，药物发现以及人类疾病的哺乳动物和非哺乳动物动物模型。除了在各自领域的研究前沿，受邀演讲者有不同的专业知识和观点。因此，会议将作为一个及时和充满活力的论坛，交流最新的数据，将产生关于MHE发病机制的新想法，方法和假设，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。 2012年11月1日至4日在费城宾夕法尼亚州，将有八个会议MHE临床表现和骨科，人类遗传学，发育生物学，硫酸乙酰肝素化学，动物疾病模型和相关的骨骼疾病，约50名参与者（包括30多名特邀演讲者和非发言讨论者）。每场会议将有三到四位发言者，他们将进行20分钟的演讲，然后进行10分钟的讨论。会议的形式、名册和规模旨在最大限度地扩大与会者在非正式场合的互动。由于硫酸乙酰肝素在人体生理学中的广泛作用，本次会议将对基础研究、转化医学和临床医学产生广泛而深远的影响。同样重要的是，它将为患者和家庭带来新的希望，即MHE正在积极研究，总有一天会找到治愈方法。 公共卫生相关性：叙述多发性遗传性外生骨疣是一种使人衰弱的遗传性疾病，其特征是形成多个骨性突起，导致大量症状和病理后果本次会议旨在促进有关MHE的最新信息的交流以及研究这种疾病的实验室之间的合作和协同作用。这一目标将通过将世界整形外科、人类遗传学、发育生物学、糖生物学和相关人类骨骼疾病领域的专家聚集在一起，并为他们提供一个高度集中的论坛来培养新的想法，促进跨学科合作，发现疾病的发病机制，并开始设想可能的治疗方法来实现。

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.