中文摘要：

目的检测一个非近亲婚配的成骨不全家系中5例患者的1型胶原α1链（COL1A1）基因突变位点。方法收集一个成骨不全家系的临床资料，每例患者采用双能X线吸收仪检测其L1～L4、股骨颈和全髋部位的骨密度（BMD），并采用聚合酶链反应及直接测序法对家系内成员及50名对照者进行COL1A1基因突变位点检测。结果根据临床表现和放射学资料，该家庭中5例患者被诊断为I型成骨不全显性遗传。该家系中成骨不全患者均存在COLIA1基因的第28外显子的两个碱基（AG）缺失造成的突变（p．Gly632x），均为杂合突变，导致632Gly之后的氨基酸编码提前终止，而在家系内正常个体及其他正常对照者中均未发现该突变。除先证者姨妈和表哥的L1～L4 BMD低于同龄正常人外，其他患者的BMD基本与同龄正常人相似。结论本研究首次发现了位于COL1A1基因第28外显子的新突变位点可导致I型成骨不全，为进一步探讨COL1A1基因型和成骨不全表型的关系提供了依据。

英文摘要：

Objective To report a novel gene mutation of collagen, type I , alpha 1 （COL1A1） in a Chinese non-consanguineous marriage family with five osteogenesis imperfecta （OI） patients. Methods We collected the clinical data of a Chinese OI family. The bone mineral densities （BMD） at the lumbar spine （L1 -L4 ） and proximal femur （Neck, and total hip） were measured by Dual energy X-ray absorptiometry in each patient. Polymerase chain reaction and DNA sequencing were used to examine the COL1A1 gene mutation in all the 5 patients and 50 normal controls. Results All the 5 patients in this family were diagnosed as OI type I with dominant inheritance according to their clinical and radiological features. Sequencing of the COL1A1 gene revealed a （AG）2 bps lost in exon 28, which leads deletion mutation and a stop codon after codon Gly632 （p. Gly632x）. All these deletion mutation were heterozygosis mutations. The mutation was not detected in the other members of the OI family and the normal controls. The BMD in the proband aunt and her sons spine was osteopenia compared to the age cohort other OI patients in the family had normal BMD. Conclusion A novel p. Gly632x mutation of COL1A1 gene at exon 28, which can cause OK, has been identified, paving a way for further understanding the phenotype-genotype correlation of COL1A1 gene. （Shanghai Med J, 2009, 32： 590-593）