【摘要】 目的通过对一个软骨发育不全(achondroplasia,ACH)家系成员成纤维细胞生长因子受体(fibroblast growth factor receptor 3,FGFR3)基因突变的靶向检测与产前基因诊断,以达到优生的目的。方法应用变性高效液相色谱技术(denaturing high performance liquid chromatography,DHPLC),PCR产物限制性片段多态分析(PCR-restricted fragment length polymorphism,PCR-RFLP)与PCR产物直接测序的方法,对ACH家系中4个表型正常个体、2个ACH患者与胎儿的FGFR3基因第10外显子中可导致G380R与G375C改变的3个热点突变进行检测。结果ACH家系中患者均为G1138A突变杂合子,而表型正常者与胎儿在该位点为GG纯合子。胎儿娩出后脐血基因分析结果与产前检查一致,且随后1年中生长发育正常。结论软骨发育不全是一种少见的常染色体显性遗传病,随着致病基因FGFR3的定位克隆,该病的临床基因检测与产前基因诊断成为可能,但仍需完善中国人ACH基因突变谱,以不断提高对该病的分子诊断水平。更多还原

【Abstract】 Objectives To perform prenatal genetic diagnosis in a achondroplasia family and thus prevent the birth of fetus with achondroplasia fibroblast growth factor receptor 3 gene(FGFR3)mutation. Methods Three hot mutations in exon 10 of FGFR3 gene,which results in amino acid changes of G380R and G375C,were detected by the denaturing high performance liquid chromatography(DHPLC),restricted fragment length polymorphism(RFLP)analysis and DNA sequencing in four normal phenotype individuals,two achondroplasia patients and a fetus. Results G1138A mutation of FGFR3 gene was observed in two patients in addition to the presence of a wild FGFR3 gene,while the normal phenotype individuals including the fetus showed two wild FGFR3 genes. The gene analysis of umbilical blood was consistent with results of amniocentesis and bone growth of the infant was normal in the following year. All three molecular detection techniques identified the presence of G1138A mutation. Conclusions Achondroplasia is a rare and inherited by autosomal dominant manner. With identification of the position and clone of candidate gene FGFR3,prenatal genetic diagnosis becomes reality by detecting FGFR3 mutation. Therefore,it is important to establish FGFR3 mutation spectrum of Chinese to further improve the ability and reliability of gene diagnosis.更多还原