PATHOPHYSIOLOGY AND TREATMENT OF HUMAN GENETIC DISEASES

我们继续进行研究，以阐明 遗传性结缔组织疾病，并将其应用于 治疗疾病的信息。 我们已经开发出一种 1型胶原mRNA点突变检测系统 通过RNA酶A消化RNA/RNA杂交体中的错配。 反义 核糖核酸探针与患者的mRNA杂交。 该系统 允许更快速的检测和更准确的定位， 突变比可能与胶原蛋白系统。 几个突变已定位在患者骨发生 目前正在测序中。 继续研究成纤维细胞的胶原蛋白， 成骨不全患者的成骨细胞允许 描绘过度修饰的程度和方向。 的 非胶原基质蛋白对成骨细胞代谢的影响 发现了一些异常 我们已经证明 绒毛膜绒毛表达相同的胶原缺陷， 成纤维细胞的OI患者;这将允许早期产前 在选定的病例中进行诊断。 在成骨不全的临床方案中，我们有 显示生长激素分泌和IGF-I异常 与身材矮小有关的刺激。 增长的初步研究 刺激是令人鼓舞的。 我们继续进行康复治疗 和支具治疗方案。

We have continued studies to elucidate the molecular basis of heritable connective tissue disorders, and to apply this information to treatment of the disease. We have developed a system for the detection of point mutatiom in Type 1 collagen mRNA by RNase A digestion of mismatches in RNA/RNA hybrids. Anti-sense riboprobe is hybridized to the mRNA of the patient. This system allows for more rapid detection and more accurate localization of mutations than had been possible with the collagen protein system. Several mutations have been localized in patients with Osteogenesis Imperfecta and are now being sequenced. Continued work on the collagen protein of fibroblasts and Osteoblasts of Osteogenesis Imperfecta patients has allowed the delineation of the extent and direction of over modification. The effect on the osteoblast metabolism of non-collagen matrix proteins has revealed some abnormalities. We have demonstrated that chorionic villi express the same collagen defect as is expressed by the fibroblasts of OI patients; this will allow earlier prenatal diagnosis in selected cases. In clinical protocols on Osteogenesis Imperfecta, we have demonstrated abnormalities of growth hormone secretion and IGF-l stimulation associated with short stature. A pilot study of growth stimulation was encouraging. We have continued our rehabilitation and bracing protocol for children with moderately severe OI.