Lanning R W, Brown C A
Hum Mutat. 1997;10(6):496-9. doi: 10.1002/(SICI)1098-1004(1997)10:6<496::AID-HUMU13>3.0.CO;2-V.
Homozygous achondroplasia is a neonatal lethal condition which can only be diagnosed in the first trimester of pregnancy by molecular analysis. The vast majority of patients with achondroplasia have a G-->A substitution at position 1138 of the fibroblast growth factor receptor (FGFR3) cDNA sequence, resulting in the substitution of an arginine for a glycine residue at position 380 of the FGFR3 protein. This mutation has typically been detected by SfcI digestion of amplified genomic DNA. We have demonstrated that the SfcI digestion protocol does not consistently distinguish between DNA samples heterozygous and homozygous for the G1138A substitution, and illustrates how the misdiagnosis of a homozygous affected fetus for one carrying only one copy of the G1138A mutation could occur. We report here an improved, simple nonradioactive technique which can reliably and consistently detect the presence of the G1138A mutation both in the heterozygous and homozygous state.
纯合性软骨发育不全是一种新生儿致死性疾病，只能在妊娠早期通过分子分析进行诊断。绝大多数软骨发育不全患者在成纤维细胞生长因子受体（FGFR3）cDNA序列的第1138位发生了G→A替换，导致FGFR3蛋白第380位的甘氨酸残基被精氨酸取代。这种突变通常通过对扩增的基因组DNA进行SfcI酶切来检测。我们已经证明，SfcI酶切方案并不能始终如一地区分G1138A替换的杂合和纯合DNA样本，并说明了仅携带一份G1138A突变的胎儿如何可能被误诊为纯合性患病胎儿。我们在此报告一种改进的、简单的非放射性技术，该技术能够可靠且一致地检测出杂合和纯合状态下G1138A突变的存在。
