Scott J E, Tenni R
Department of Chemical Morphology, Manchester University, UK.
Cell Biochem Funct. 1997 Dec;15(4):283-6. doi: 10.1002/(SICI)1099-0844(199712)15:4<283::AID-CBF752>3.0.CO;2-B.
Osteogenesis imperfecta (OI) is a disease characterized by bone malformations caused by mutations in type 1 collagen. Since many of the 338 possible glycine mutations have not been observed in clinical practice, is this due to chance alone? Because only 83 mutations have been reported in 126 patients, we conclude that many mutations are absent from clinical data for non-random causes. Mutations affecting vital intermolecular interactions in the extracellular matrix (e.g. potential collagen binding sites for proteoglycans) may result in non-viable fetuses that do not progress to clinical status. Some mutations may be silent because they do not significantly affect normal function. The total number of clinically active mutations that will be observed may be far fewer than the potential 338 maximum.
成骨不全症（OI）是一种由1型胶原蛋白突变导致骨畸形的疾病。由于在临床实践中尚未观察到338种可能的甘氨酸突变中的许多种，这仅仅是偶然原因吗？因为在126名患者中仅报告了83种突变，我们得出结论，许多突变由于非随机原因而未出现在临床数据中。影响细胞外基质中重要分子间相互作用的突变（例如蛋白聚糖的潜在胶原蛋白结合位点）可能导致无法存活的胎儿，这些胎儿无法发展到临床阶段。一些突变可能是沉默的，因为它们不会显著影响正常功能。实际观察到的具有临床活性的突变总数可能远少于潜在的338种最大值。
