Mutation Analysis of COL1A1 and COL1A2 in Patients Diagnosed With Osteogenesis Imperfecta Type I-IV
Mutation Analysis of COL1A1 and COL1A2 in Patients Diagnosed With Osteogenesis Imperfecta Type I-IV
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DOI：
10.1002/humu.9430
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发表时间：
2006-07-01
期刊：
影响因子：
3.9
通讯作者：
Dalton, Ann
中科院分区：
文献类型：
--
作者：
Pollitt, Rebecca;McMahon, Robert;Dalton, Ann
成骨不全症（Osteogenesis Imperfecta， OI）是一种异质性的遗传性疾病，其特征是骨脆性增加，临床严重程度从轻微到致命不等。迄今为止，根据临床表型和组织学发现，已经描述了七种类型的成骨不全。大多数临床诊断为I- iv型成骨不全的患者都有COL1A1或COL1A2基因突变，这些基因编码I型胶原蛋白的两条α链，这是骨基质的主要成分。对83例I-IV型不相关OI患者的COL1A1和COL1A2进行分析，共发现62个突变。38个是新的，26个在COL1A1中，12个在COL1A2中，这些在这里描述。最大的一组由影响两条α链三螺旋结构域甘氨酸残基的点突变组成，预计会破坏蛋白质的折叠和结构。这与之前公布的数据一致。本文描述了一个双重GC缺失，一个不寻常的398碱基缺失，预计将完全去除COL1A2的外显子20，以及一个导致c端前肽中保守半胱氨酸取代的点突变。此外，在c -前肽和n端信号肽的切割位点的罕见突变被描述。(C) 2006 Wiley-Liss, Inc。
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. (C) 2006 Wiley-Liss, Inc.