PATHOPHYSIOLOGY AND TREATMENT OF HUMAN GENETIC DISEASES

我们一直在继续研究，以阐明 遗传性结缔组织疾病，并将其应用于 关于治疗这种疾病的信息。我们已经开发出一种 一种检测1型胶原基因点突变的系统 通过核糖核酸酶A消化RNA/RNA杂交物中的错配。反义的 核探针与患者的mRNA杂交。这个系统 允许更快速地检测和更准确地定位 比胶原蛋白系统可能发生的突变更多。 在成骨患者中已经定位了几个突变 并不完美，现在正在测序。 继续研究成纤维细胞的胶原蛋白和 成骨不全患者的成骨细胞使 划定过度修改的程度和方向。这个 非胶原基质蛋白对成骨细胞代谢的影响 揭示了一些反常现象。我们已经证明了 绒毛表达与表达相同的胶原蛋白缺陷 OI患者的成纤维细胞；这将使更早的产前 在选定病例中进行诊断。 在成骨不全的临床方案中，我们有 生长激素分泌异常与胰岛素样生长因子-L 与矮小有关的刺激。一项关于成长的初步研究 刺激是鼓舞人心的。我们仍在继续康复 以及为患有中度严重OI的儿童制定的支撑方案。

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.