GENETICS OF DEVELOPMENTAL DYSPLASIA OF THE HIP

髋关节发育不良的遗传学

• 批准号: 7380758
• 负责人: INGRID A HOLM
• 金额: $ 3.03万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380758
• 关键词: GENETICS; DEVELOPMENTAL; DYSPLASIA; HIP

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims/Objectives Developmental dysplasia of the hip (DDH) is a common disease of early childhood in which the normal seating of the femoral head in the acetabulum is disrupted. DDH is manifested in several ways in the pediatric patient, ranging from mild instability of the femoral head with slight capsular laxity, to moderate lateral displacement of the femoral head without loss of contact of the head with the acetabulum, to complete dislocation of the femoral head from the acetabulum [1]. Although the incident is felt to vary from one to four per 1,000 births, an incidence of up to 13 per 1,000 has been reported [2]. There is a strong genetic component to DDH, with a polygenic component felt to be responsible for the acetabular dysplasia, and a monogenic component felt to be responsible for the lax joint capsule [14]. There is also evidence suggesting a relatively high rate of generalized joint laxity (GJL) in patients with DDH, and defects in collagen have been found in patients with GJL [11-14, 15-20]. Moreover, a recent genetic association study has shown evidence for an association between DDH and a collagen gene [25]. We hypothesize that the association between DDH and collagen genes is strongest in children with GJL, and if we subgroup patients with DDH based on the presence or absence of GJL we will be able to identify genes associated with DDH in the subgroup with GJL. We also hypothesize that the subgroup of patients with GJL will demonstrate a pattern of inheritance that is close to Mendelian, whereas those without GJl will show a multifactorial inheritance pattern. The findings from this study will improve our understanding of the pathogenesis of DDH, allow us to provide more accurate genetic counseling, and may allow the targeting of therapies based on the uderlying etiology.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。特定目的/目的发育性髋关节发育不良（DDH）是儿童早期的常见疾病，其中股骨头在髋臼中的正常就座被破坏。DDH在儿科患者中表现为几种方式，从股骨头轻度不稳定伴轻微关节囊松弛，到股骨头中度外侧移位而股骨头与髋臼接触丧失，再到股骨头与髋臼完全脱位[1]。虽然这一事件的发生率在每1,000名新生儿中有1到4人不等，但据报道，每1,000名新生儿中有13人发生[2]。DDH有很强的遗传成分，多基因成分被认为是髋臼发育不良的原因，单基因成分被认为是关节囊松弛的原因[14]。还有证据表明DDH患者的全身关节松弛（GJL）发生率相对较高，并且在GJL患者中发现胶原蛋白缺陷[11-14，15-20]。此外，最近的一项遗传关联研究表明DDH与胶原蛋白基因之间存在关联[25]。我们假设DDH和胶原基因之间的关联在GJL儿童中最强，如果我们根据GJL的存在或不存在对DDH患者进行亚组，我们将能够在GJL亚组中识别与DDH相关的基因。我们还假设患有GJL的患者亚组将表现出接近孟德尔的遗传模式，而那些没有GJl的患者将显示多因子遗传模式。这项研究的结果将提高我们对DDH发病机制的理解，使我们能够提供更准确的遗传咨询，并可能允许基于未知病因的靶向治疗。