HERITABLE DISORDERS OF CONNECTIVE TISSUE

该部门继续进行旨在阐明分子的研究。 结缔组织遗传性疾病的机制，特别是 成骨不全)和Ehler-Danlos综合征(EDS)，以及 将这些信息应用于这些疾病的治疗。 该科的主要目标之一是确定 I型胶原突变的类型和位置与 骨病的严重程度。为此，我们应用了我们的胶原蛋白 蛋白质和RNA杂交法治疗4例OI 严肃性。我们已经证明了丝氨酸对甘氨酸的取代作用 沿着两条胶原链的不同位置。我们已经提出了一个 具有交替性的OI病理生理区域模型 沿着致命性和非致命性突变的链条。在这 模式，区域的功能意义在于更高 有序纤维，对成骨细胞新陈代谢的次要影响 与非胶原基质分子的相互作用。 我们研究了7例轻中度EDS，发现 这些病例的胶原蛋白结果与OI研究结果一致。那是, EDS患者具有类似于OI的胶原蛋白异常 案子。由于EDS和OI的症状是重叠的，除了EDS 患者没有脆性骨病和骨质疏松，这些病例 提供对非关键胶原蛋白区域的重要洞察 对于骨骼结构。我们正在进行这些基因的分子描述 3例采用SSCP分析。 在临床研究中，我们启动了一项生长激素治疗试验 患有OI的矮小儿童将确定其对线性生长的影响， 骨密度和骨形态计量学特性。我们正在结束一项 OI儿童脱机的协作性交叉方案。 我们正在探索新的碳棒和聚合物棒材料。

The section has continued its studies aimed at elucidating the molecular mechanisms of heritable disorders of connective tissue, specifically osteogenesis imperfecta OI) and Ehlers-Danlos syndrome (EDS), and to apply this information to the treatment of these disorders. One of the primary goals of the Section is to determine the relationship between the type and location of the type I collagen mutation and the severity of the bone disease. To this end, we have applied our collagen protein and RNA hybrid methodology to four cases of OI with a range of severities. We have demonstrated serine for glycine substitutions at different positions along the two collagen chains. We have proposed a regional model of OI pathophysiology in which there is an alternation along the chains of clusters of lethal and non-lethal mutations. In this model, the functional significance of the regions resides in higher order fibrils, secondary effects on osteoblast metabolism or interactions with no-collagenous matrix molecules. We have studied seven cases of mild-moderate EDS, and find that the collagen results in these cases converge with the OI studies. That is, the EDS cases have abnormalities of collagen protein similar to OI cases. Since the symptoms of EDS and OI overlap, except that EDS patients do not have brittle bone disease and osteoporosis, these cases provide important insight into regions of collagen which are non-crucial for bone structure. We are pursuing the molecular description of these cases using SSCP analysis. In clinical studies, we initiated a treatment trial of growth hormone in short children with OI and will determine its effects on linear growth, bone density and bone morphometric properties. We are concluding a collaborative cross-over protocol for weaning OI children from braces. We are exploring new carbon and polymer rodding materials.