成骨不全家系一个新的Ⅰ型胶原α1链蛋白基因突变

目的 对Ⅰ型胶原α1链蛋白基因（COL1A1基因）进行测序研究，旨在寻找已知或未知的COL1A1基因突变位点，探讨我国成骨不全的发病机制。方法 研究一常染色体显性遗传成骨不全家系的临床特征，设计引物对家系中患者和正常人的COL1A1基因外显子进行扩增和测序分析，同时对群体中无血缘关系的50名健康对照者进行限制性内切酶分析。结果 发现家系中成骨不全患者COL1A1基因的第3470位点的碱基G→A的突变，导致G1157D，而在家系内非患者及正常对照者中均无发现。结论 COL1A1基因突变也是中国人群中成骨不全致病原因之一，现发现的突变属成骨不全一个新的致病基因突变。甘氨酸转变成天冬氨酸的这种突变对成骨不全表型具有重要的影响。

A new mutation in COL1A1 gene in a family with osteogenesis imperfecta

Objective Osteogenesis imperfecta (OI) is a congenital disease of connective tissue of increased bone fragility and low bone mass, most often caused by single amino acid substitution of glycine residues in the collagen, type I, alpha 1 protein (COL1A1)gene or the collagen, type I, alpha 2 protein(COL1A2)gene, encoding type I procollagen chains. We describe here the clinical, biochemical, and molecular characterization of a family with type I OI in China and would like to explore whether the biochemical characterization of OI in China is different from that in other countries. Methods Through clinical research,we study the clinical characteristic of the OI household. Genomic DNA was isolated from peripheral blood lymphocytes of the proband and his family members by saturation hydroxybenzene- chloroform methods; amplification of target COL1A1 gene by Polymerase chain reaction with 23 pairs of different primers; purification;direct sequencing of the Polymerase chain reaction product. According to the mutation site,we took restriction enzyme analysis to 50 normal control people. Results We found a G and A heterozygosis mutation at the exon 48 causing an a1(I) p.G1157D substitution in the proband and his sister who is also a sufferer of OI. At the same time,other normal people in the family and other normal control people do not have this change. Conclusion This is the first delineation of an aspartic acid substitution in new site of the a1(I) chain causing nonlethal osteogenesis imperfecta. Only nine aspartic acid substitution in type I collagen has been fully reported in the world. Now we revealed a new nosogenesis of OI. Since only few of nucleotide changes in type I collagen glycine codons would result in an aspartic acid substitution,these are predicted to be infrequent. Furthermore,it is possible to suggest that nosogenesis of OI in china is different from other countries.