Pollitt Rebecca, McMahon Robert, Nunn Janice, Bamford Robert, Afifi Amal, Bishop Nicholas, Dalton Ann
Sheffield Molecular Genetics Service, Sheffield Children's NHS Trust, Sheffield, United Kingdom.
Hum Mutat. 2006 Jul;27(7):716. doi: 10.1002/humu.9430.
Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. To date, seven types of OI have been described, based on clinical phenotype and histological findings. Most patients with a clinical diagnosis of OI type I-IV have a mutation in the COL1A1 or COL1A2 genes which encode the two alpha chains of type I collagen, the major component of the bone matrix. Analysis of COL1A1 and COL1A2 in a cohort of 83 unrelated patients with OI type I-IV identified a total of 62 mutations. Thirty-eight appear novel, 26 in COL1A1, and 12 in COL1A2, and these are described here. The largest group consists of point mutations affecting glycine residues in the triple helical domain of the two alpha chains, predicted to disrupt protein folding and structure. This is in accordance with previously published data. A doublet GC deletion, an unusual 398 base deletion predicted to completely remove exon 20 of COL1A2, and a point mutation resulting in substitution of a conserved cysteine in the C-terminal propeptide are described. In addition rare mutations at the cleavage sites of the C-propeptide and the N-terminal signal peptide are described.
成骨不全症（OI）是一组遗传性疾病的统称，其特征为骨脆性增加，临床严重程度从轻度到致命不等。迄今为止，根据临床表型和组织学发现，已描述了七种类型的OI。大多数临床诊断为I-IV型OI的患者，其编码I型胶原蛋白（骨基质的主要成分）两条α链的COL1A1或COL1A2基因发生了突变。对83名无关的I-IV型OI患者进行COL1A1和COL1A2分析，共鉴定出62个突变。其中38个似乎是新突变，COL1A1中有26个，COL1A2中有12个，本文对此进行了描述。最大的一组是影响两条α链三螺旋结构域中甘氨酸残基的点突变，预计会破坏蛋白质折叠和结构。这与先前发表的数据一致。本文还描述了一个GC双联体缺失、一个预计会完全去除COL1A2第20外显子的异常398碱基缺失，以及一个导致C末端前肽中保守半胱氨酸被取代的点突变。此外，还描述了C前肽和N末端信号肽切割位点的罕见突变。
