CLINICAL & GENETIC STUDIES OF AUTOSOMAL DOMINANT OSTEOPETROSIS

2型常染色体显性骨硬化症（ADO 2）是一种遗传性疾病，由破骨细胞介导的骨吸收失败引起。虽然ADO 2患者的骨密度增加，但骨质量差，骨折风险增加。 这种疾病的发病率为75%，因此存在不具有这种疾病的典型放射学表现的“携带者”。 然而，敏感的方法还没有被用来确定是否载体在破骨细胞功能的微妙缺陷。 虽然ADO 2是由于破骨细胞介导的骨吸收的失败，但该疾病的发病机制知之甚少，并且没有该疾病的动物模型。 本研究的目的是进一步描述该疾病的临床表现，并使用定位克隆技术确定该疾病的基因。 为了实现我们的目标，我们将1）从ADO 2家族成员中进行表型表征并获得血液用于生化和DNA研究; 2）以高分辨率绘制疾病基因图; 3）分离并克隆基因。 该基因的鉴定将提供深入了解ADO 2的病理生理学，以及提供深入了解破骨细胞的调节和功能。

Type 2 autosomal dominant osteopetrosis (ADO2) is an inherited disorder that results from a failure in osteoclast mediated bone resorption. Although ADO2 patients have increased bone mineral density, the bone is of poor quality and they are at increased risk for fracture. The disease has a 75% penetrance, thus "carriers" exist that do not have the typical radiographic manifestations of the disorder. However, sensitive methods have not been used to determine if carriers have subtle defects in osteoclast function. Although ADO2 is due to a failure of osteoclast mediated bone resorption, the pathogenesis of the disorder is poorly understood and there are no animal models of the disorder. The goals of the present study are to further characterize the clinical manifestations of the disorder and to identify the gene responsible for the disorder using positional cloning techniques. To accomplish our goal we will 1) phenotypically characterize and obtain blood for biochemical and DNA studies from ADO2 family members; 2) map the disease gene with high resolution and 3) isolate and clone the gene. Identification of the gene will provide insight into the pathophysiology of ADO2 as well as provide insight into osteoclast regulation and function.