中文摘要：

为了揭示成骨不全（Osteogenesis imperfecta, OI）Ⅰ型家系的分子遗传学发生机制，文章采用PCR-DNA直接测序法，对患儿 COL1A1和 COL1A2基因共103个外显子（E）进行突变检测。结果显示：患儿 COL1A1基因未发现任何病理性突变，而在 COL1A2基因 E19内发现一新的杂合错义突变（p.G316C），该突变来自其父，而其母正常，其他表型正常的6位亲属也均未发现该突变；通过 DHPLC（Denaturing high performance uid chromatography）筛检，发现患儿与其父均有异常双峰，而其母和所有正常对照均为正常单峰；通过ASA（Allele specific amplification）筛检，患儿与其父均有391 bp的特异扩增带，而其母和所有正常对照均未见特异扩增带；保守性分析结果显示，该突变位点所在甘氨酸在进化上具有高度保守性；SIFT和 PolyPhen-2软件预测结果显示，新突变造成的结果是“有害的”和“很可能有害”。上述结果均说明 COL1A2基因c.946G〉T/p.G316C新突变是导致OI-Ⅰ型的致病性突变，是引起患儿发病的真正内因。患儿父母若再次孕育，可在孕早期进行产前基因诊断或孕前期进行PGD（Preimplantation genetic diagnosis）予以防患。

英文摘要：

To uncover the molecular pathogenic mechanism of congenital osteogenesis imperfecta （OI） type I, all the 103 exons of the COL1A1 （Collagen, type Ⅰ, alpha 1） and COL1A2 （Collagen, type Ⅰ, alpha 2） genes in a child with OI type Ⅰ were screened using PCR-DNA direct sequencing. The results showed no pathological mutation in COL1A1＆amp;nbsp;gene, but a novel mutation c.946G〉T/p.G316C in the exon 19 of COL1A2 gene, which was inherited from her father. This mutation was not found in her mother and other six phenotypically normal relatives. By denaturing high perfor-mance liquid chromatography （DHPLC） screening, the abnormal double-peak was visualized in PCR products of exon 19 of COL1A2 gene in the proband and her father, while the normal single-peak was shown in those of her mother and all the healthy controls. Using allele specific amplification （ASA） screening, a specific band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her father, but not in other samples. The amino acid encoded by the mutation site is evolutionarily highly conserved, and this mutation was a“damaging”or“probably damaging”factor to OI type Ⅰ, based on the predicting results using SIFT and Polyphen-2 softwares. In conclusion, the novel c.946G〉T/p.G316C mutation in COL1A2 gene is a pathogenic mutation that could result in OI type Ⅰ. If the couple wants to get pregnant again, it is necessary to screen the mutation site in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or through preimplantation genetic diagnosis （PGD） in the progestation.