For growth factor-receptor system molecules target, a development study of genetic diagnosis and treatment in oral ＆ maxilla-facial disease

成纤维细胞生长因子受体(FGFR)基因的等位基因突变在Apert、Pfeiffer、Crouzon综合征软骨发育不全等疾病中起主导作用。本实验室对4例Crouzon综合征患者和A例软骨发育不全患者的FGFR2第三免疫球蛋白结构域和FGFR3跨膜区的序列进行了单链构象多态性分析和直接测序。我们发现了4个新的FGFR2突变，与多种表型相关，从细小到严重不等。结果如下：病例1：2日龄雌性，76日龄进行V-P分流术，160日龄进行颅骨成形术。目前状况：脑积水，前额叶显著肿胀，轻度脑水肿，外翻。临床诊断：克劳松综合征(重度)GE…更多诊断：Leu343Met[FGFR2(成纤维细胞生长因子结合结构域)突变]病例2：2岁女性目前患病：2岁时进行颅骨成形术目前状态：腭部高位，先天畸形，性心理发育延迟，对症临床诊断：Crouzon综合征(重度)基因诊断：Glu289Pro[FGFR2(成纤维细胞生长因子结合结构域)突变]病例3：13.5岁男性目前疾病：13岁时接受颅骨成形术目前状况：腭部高位，先天畸形，外展临床诊断：Crouzon综合征(轻度)基因诊断：Ser354 Phe[FGFR2(第三免疫球蛋白TM线性域突变)]病例4：7岁男性目前病情：未做颅骨成形术现状：腭部高位、后遗症、上颌骨突出临床诊断：Crouzon综合征(细长)基因诊断：Leu246+T[FGFR2(第二和第三个免疫球蛋白连接结构域)突变]病例5：11个月大。现症：37周龄V-P分流术现症：脑积水、前额显著肿胀、病理性股骨骨折、三叉神经手、寰枢椎松动临床诊断：骨质疏松症基因诊断：软骨发育不全[FGFR3(跨膜区突变)突变]较少

Dominantly acting, allelic mutations of the fibroblast growth factor receptor (FGFR) gene have been described in Apert, Pfeiffer, crouzon syndrome achondroplasia and so on. FGFRs regulate cell proliferation, differentiation and migration in bone and cartilage tissue through complex signaling pathway.In our laboratory, 4 patients with Crouzon syndrome and A patients with a achondroplasia were analyzed for sequence in the third immunoglobulin domain of FGFR2 and transmembrane domain of FGFR3 using single strand conformation polymorphism analysis (SSCP) and direct-sequencing. We have identified 4 novel mutations of FGFR2 associates with a wide range of phenotypes, ranging from slightness to severe.In the result follows ;Case1 : 2 days old female Present illness : V-P shunt operation at 76 days old, Cranioplasty operation at 160 days oldPresent status : Hydrocephalus, Remarkable swelling of anterior frontanel, slight brain edema, ExophthaimosClinical Diagnosis : Crouzon syndrome (severe)Ge … More ne Diagnosis : Leu343Met [FGFR2 (FGF binding domain) mutation]Case2 : 2 years old female Present illness: Cranioplasty operation at 2 years oldPresent status : High position of palates, Progenie, Delayed psychosexual development, LogopathyClinical Diagnosis : Crouzon syndrome (severe)Gene Diagnosis : Glu289Pro [FGFR2 (FGF binding domain) mutation]Case3 : 13.5 years old male Present illness : Cranioplasty operation at 13 years oldPresent status : High position of palates, Progenie, ExophalmosClinical Diagnosis : Crouzon syndrome (mild)Gene Diagnosis : Ser354Phe [FGFR2 (the third immunoglobulin-TM linker domain) mutation]Case4 : 7 years old male. Present illness: no Cranioplasty operationPresent status : High position of palates, Progenie, ExophalmosClinical Diagnosis : Crouzon syndrome (slightness)Gene Diagnosis : Leu246+T [FGFR2 (the second and third immunoglobulin linker domain) mutation]Case5 : 11 months old male. Present illness: V-P shunt operation at 37 weeks oldPresent status : Hydrocephalus, Remarkable swelling of anterior frontanel, pathologic femoral fracture, Trident hands, Atlanto-axial laxationClinical Diagnosis : DysosteogenesisGene Diagnosis : Achondroplasia [FGFR3 (Transmembrane domain mutation) mutation] Less