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（fibroblast growth factor receptor，FGFR）基因的显性、等位基因突变已在Apert、Pfeiffer、crouzon综合征等软骨发育不全中被描述，FGFR通过复杂的信号通路调节骨和软骨组织中细胞的增殖、分化和迁移。分析了4例Crouzon综合征患者和1例软骨发育不全患者的FGFR 2第三免疫球蛋白结构域和FGFR 2跨膜结构域的序列。采用单链构象多态性分析（SSCP）和直接测序法检测FGFR3。我们发现了4个新的FGFR2突变，与从轻微到严重的广泛表型相关。结果如下：病例1：2日龄女性目前疾病：76日龄V-P分流术，160日龄颅骨成形术目前状态：脑积水，前额叶明显肿胀，轻度脑水肿，突眼临床诊断：Crouzon综合征（重度） ...更多信息 诊断：Leu343Met [FGFR 2例2：女，2岁，现患疾病：2岁时颅骨成形术现患状况：腭高位、先生、性心理发育延迟、精神病临床诊断：Crouzon综合征（重度）基因诊断：Glu289Pro [FGFR2（FGF结合域）突变]病例3：13.5岁男性现患疾病：13岁颅骨成形术现状态：腭高位，子代，外翻临床诊断：Crouzon综合征（轻度）基因诊断：Ser354Phe [FGFR2（第三免疫球蛋白-TM连接结构域）突变]病例4：7岁男性。当前疾病：无颅骨成形术现状：腭高位，先天性，外翻临床诊断：Crouzon综合征（身材苗条）基因诊断：Leu246 + T [FGFR2（第二和第三免疫球蛋白连接结构域）突变]病例5：11个月男性。当前疾病：37周龄时接受V-P分流术目前状况：脑积水，前额叶显著肿胀，病理性股骨骨折，三叉戟手，枢椎松弛临床诊断：成骨不良基因诊断：软骨发育不全[FGFR3（跨膜结构域突变）突变]减

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