GENETICS OF DEVELOPMENTAL DYSPLASIA OF THE HIP

髋关节发育不良的遗传学

• 批准号: 7607269
• 负责人: INGRID A HOLM
• 金额: $ 3.91万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607269
• 关键词: Birth; Child; Childhood; Collagen; Collagen Gene; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Disease; Dysplasia; Etiology; Funding; Genes; Genetic; Genetic Counseling; Grant; Head; Hip region structure; Incidence; Inheritance Patterns; Institution; Joint Capsule; Joint Dislocation; Joint Laxity; Lateral; Multifactorial Inheritance; Pathogenesis; Patients; Range; Rate; Reporting; Research; Research Personnel; Resources; Source; Subgroup; United States National Institutes of Health; acetabulum; base; developmental genetics; early childhood; genetic association; improved

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. Although the incidence is felt to vary from one to four per 1,000 births, an incidence of up to 13 per 1,000 has been reported. 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. 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. Moreover, a recent genetic association study has shown evidence for an association between DDH and a collagen gene. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 具体目的/目标 发育性髋关节发育不良（DDH）是幼儿期的一种常见疾病，股骨头在髋臼中的正常就位被破坏。 DDH 在儿科患者中以多种方式表现，从股骨头轻度不稳定伴轻微的囊膜松弛，到股骨头中度侧向移位但不失去股骨头与髋臼的接触，再到股骨头从髋臼完全脱位。 尽管据认为发病率从每 1,000 名新生儿 1 到 4 例不等，但据报道，发病率高达每 1,000 名新生儿 13 例。 DDH 有很强的遗传因素，其中多基因成分被认为是导致髋臼发育不良的原因，而单基因成分被认为是导致关节囊松弛的原因。 还有证据表明，DDH 患者全身性关节松弛 (GJL) 的发生率相对较高，并且在 GJL 患者中发现了胶原蛋白缺陷。 此外，最近的一项遗传关联研究显示了 DDH 与胶原蛋白基因之间关联的证据。 我们假设 DDH 和胶原蛋白基因之间的关联在 GJL 儿童中最强，如果我们根据 GJL 存在或不存在对 DDH 患者进行分组，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遗传模式，而那些没有 GJ1 的患者将表现出多因素遗传模式。 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，并可能允许根据深层病因进行靶向治疗。