软骨发育不全患儿FGFR3基因突变的检测

Detection of FGFR3 gene mutation in achondroplasia

为了解软骨发育不全基因突变类型，采用聚合酶链反应－限制性酶切分析的方法，对１２例软骨发育不全患者、２例散发患者的父母和４例健康正常人的成纤维细胞生长因子受体３（ＦＧＦＲ３）基因位点的点突变进行检测。结果显示，１２例患者１１例为ＦＧＦＲ３基因跨膜区１１３８位核苷酸Ｇ→Ａ的转换，１例为Ｇ→Ｃ的颠换，均导致３８０位密码子的错义突变，即由精氨酸替代了甘氨酸。２例散发患者的父母和４例健康正常人未发现突变。结论：软骨发育不全患者出现ＦＧＦＲ３基因跨膜区的点突变，３８０位密码子是软骨发育不全患者突变的热点。

To determine gene mutations of achondroplasia in Chinese and establish a simple, rapid, sensitive and specific molecular diagnostic method, the mutations of the fibroblast growth factor receptor 3 (FGFR3) gene of 12 patients with achondroplasia, the parents of 2 sporadic cases, and 4 normal controls wereassayed by polymerase chain reactionrestriction enzyme analysis. The results showed that 11 patients had G→A transition at nucleotide 1138 in the transmembrane domain of FGFR3 and another had G→C transversion at the same locus. Both misscnse mutation resulted in the substitution of an arginine residue for a glycine at position 380 of the mature protein. No mutation was found in the parents of the 2 sporadic cases and the 4 normal controls. The conclution is that the achondroplasia patients have point mutation in the transmembrane domain of FGFR3 and the codon 380 is the hotspot of the mutation.