Ward L M, Lalic L, Roughley P J, Glorieux F H
Genetics Unit, Shriners Hospital for Children, Montréal, Québec, Canada.
Hum Mutat. 2001 May;17(5):434. doi: 10.1002/humu.1124.
Osteogenesis imperfecta (OI) is a heritable disease of bone characterized by low bone mass and bone fragility. Six different types of OI have been described to date, based on clinical phenotype and histological findings. The genetic defect in many patients with OI types I-IV is due to mutations in the genes encoding type I collagen, while patients with OI types V and VI show no evidence of mutations in the COL1A1/COL1A2 genes. Here we report thirty-three novel mutations in patients with types I-IV OI. Sixteen mutations were in COL1A1 and seventeen were in COL1A2. Most mutations resulted in substitutions for glycine: one of these, a doublet GG>CC transversion, created a unique Gly-->Pro missense mutation in the triple helical domain of COL1A2. Two rare triple helical Gly-->Glu substitutions in COL1A2 are also described. In addition, there were six single-base deletion mutations resulting in frameshifts, seven splice junction mutations, and a 9-bp triple helix insertion associated with a severe (OI II) phenotype. The variety of mutations described in the COL1A1/COL1A2 genes giving rise to an OI phenotype is in accordance with the clinical heterogeneity of the disease. Hum Mutat 17:434, 2001.
成骨不全症（OI）是一种遗传性骨病，其特征为骨量低和骨脆性增加。根据临床表型和组织学发现，迄今已描述了六种不同类型的OI。I - IV型OI的许多患者的基因缺陷是由于编码I型胶原蛋白的基因突变所致，而V型和VI型OI患者未显示COL1A1/COL1A2基因存在突变的证据。在此，我们报告了I - IV型OI患者中的33种新突变。16种突变位于COL1A1，17种突变位于COL1A2。大多数突变导致甘氨酸被替代：其中之一，一个GG>CC的双碱基颠换，在COL1A2的三螺旋结构域中产生了一个独特的Gly→Pro错义突变。还描述了COL1A2中两种罕见的三螺旋Gly→Glu替代。此外，有6种单碱基缺失突变导致移码，7种剪接连接突变，以及一个与严重（OI II）表型相关的9碱基三螺旋插入。COL1A1/COL1A2基因中导致OI表型的多种突变与该疾病的临床异质性相符。《人类突变》17:434，2001年。
