产前诊断胎儿骨骼畸形FGFR3合并FLNB基因突变1例及文献学习(1)
[摘要] 目的 分析胎儿软骨发育不全的超声、放射线表现及基因检测，提高胎儿软骨发育不全的产前诊断，研究基因-表型关系，为临床遗传咨询提供指导。方法 分析该院2018年收治的1例胎儿骨骼发育异常的病例，同时进行相关文献学习。结果 ①超声提示胎儿BPD及HC大于相应孕周2SD，FL及HL均小于相应孕周4SD以上，前额饱满，羊水过多。②胎儿染色体正常，胎儿全外显子基因检出 FGFR3 基因致病性突变及FLNB 基因杂合变异。③引产胎儿放射线检查提示前额饱满、头颅较大、四肢短小、胸廓狭窄。结论 通过超聲检查、放射线检查、染色体及全外显子测序，诊断1例ACH病例，检出FLNB基因新发位点突变，不排除为AO1的发病位点，为骨骼发育不良的基因谱提供借鉴，为临床遗传咨询提供指导。
[关键词] 产前诊断;软骨发育不全;成骨不全症I型;FGFR3基因;FLNB基因
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2020)10(b)-0043-03
[Abstract] Objective To analyze the ultrasound， radiographic and genetic testing of fetal achondroplasia， improve the prenatal diagnosis of fetal achondroplasia， study the gene-phenotype relationship， and provide guidance for clinical genetic counseling. Methods To analyze a case of fetal skeletal dysplasia admitted to the hospital in 2018， and conduct related literature study. Results 1.Ultrasound showed that the fetus's BPD and HC were greater than 2SD of the corresponding gestational week， FL and HL were both less than 4SD of the corresponding gestational week， the forehead was full， and the amniotic fluid was excessive. 2.The chromosomes of the fetus are normal， and pathogenic mutations in the FGFR3 gene and heterozygous mutations in the FLNB gene are detected in the fetal entire exon genes. 3. Radiographic examination of the induced fetus showed a full forehead， a large head， short limbs， and a narrow thorax. Conclusion The study diagnosed an ACH case through ultrasound， radiography， chromosome and whole-exome sequencing， and detected a new mutation in the FLNB gene， which is not excluded as the onset of AO1， which is a gene for skeletal dysplasia spectrum provides reference and guidance for clinical genetic counseling.
[Key words] Prenatal diagnosis; Achondroplasia; Osteogenesis Imperfecta type I; FGFR3 gene; FLNB gene
超声检查是检测胎儿骨骼异常的主要手段，不同骨骼畸形疾病超声下骨骼异常表现互相重叠，有些骨骼畸形单纯通过超声检查难以鉴别诊断，基因诊断是某些骨骼畸形疾病诊断的最佳标准。软骨发育不全(ACH，achondroplasia)是最常见的遗传性侏儒症，为常染色体显性遗传骨骼疾病，由于纤维细胞生长因子受体3(fibroblast growth factor receptor 3，FGFR3)缺陷引起，FGFR3基因位于染色体4p16.3，其不同结构功能区域的基因突变可引起不同的骨骼发育不良性疾病。骨发育不全症(atelosteogenesis，AO )I型，为常染色体显性遗传疾病，主要累及骨骼关节系统，与FLNB基因(filamin B，beta)的突变相关，FLNB基因位于染色体3p14.3，编码B细丝蛋白(FILAMIN， BETA)，是一种肌动蛋白结合蛋白，与多种受体和细胞内蛋白相互作用，调节细胞骨架依赖细胞的增殖、分化和迁移。该文分析该院2018年3月收治的1例产前超声诊断骨骼畸形胎儿，通过基因检测检出胎儿为ACH，不排除合并AO1，通过文献学习，研究基因-表型关系，为临床遗传咨询提供指导。
1 资料与方法
1.1 资料来源
厦门大学附属第一医院2018年3月收治1例胎儿骨骼发育异常病例。
1.2 方法, 百拇医药(商梅娇 汪燕)
[关键词] 产前诊断;软骨发育不全;成骨不全症I型;FGFR3基因;FLNB基因
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2020)10(b)-0043-03
[Abstract] Objective To analyze the ultrasound， radiographic and genetic testing of fetal achondroplasia， improve the prenatal diagnosis of fetal achondroplasia， study the gene-phenotype relationship， and provide guidance for clinical genetic counseling. Methods To analyze a case of fetal skeletal dysplasia admitted to the hospital in 2018， and conduct related literature study. Results 1.Ultrasound showed that the fetus's BPD and HC were greater than 2SD of the corresponding gestational week， FL and HL were both less than 4SD of the corresponding gestational week， the forehead was full， and the amniotic fluid was excessive. 2.The chromosomes of the fetus are normal， and pathogenic mutations in the FGFR3 gene and heterozygous mutations in the FLNB gene are detected in the fetal entire exon genes. 3. Radiographic examination of the induced fetus showed a full forehead， a large head， short limbs， and a narrow thorax. Conclusion The study diagnosed an ACH case through ultrasound， radiography， chromosome and whole-exome sequencing， and detected a new mutation in the FLNB gene， which is not excluded as the onset of AO1， which is a gene for skeletal dysplasia spectrum provides reference and guidance for clinical genetic counseling.
[Key words] Prenatal diagnosis; Achondroplasia; Osteogenesis Imperfecta type I; FGFR3 gene; FLNB gene
超声检查是检测胎儿骨骼异常的主要手段，不同骨骼畸形疾病超声下骨骼异常表现互相重叠，有些骨骼畸形单纯通过超声检查难以鉴别诊断，基因诊断是某些骨骼畸形疾病诊断的最佳标准。软骨发育不全(ACH，achondroplasia)是最常见的遗传性侏儒症，为常染色体显性遗传骨骼疾病，由于纤维细胞生长因子受体3(fibroblast growth factor receptor 3，FGFR3)缺陷引起，FGFR3基因位于染色体4p16.3，其不同结构功能区域的基因突变可引起不同的骨骼发育不良性疾病。骨发育不全症(atelosteogenesis，AO )I型，为常染色体显性遗传疾病，主要累及骨骼关节系统，与FLNB基因(filamin B，beta)的突变相关，FLNB基因位于染色体3p14.3，编码B细丝蛋白(FILAMIN， BETA)，是一种肌动蛋白结合蛋白，与多种受体和细胞内蛋白相互作用，调节细胞骨架依赖细胞的增殖、分化和迁移。该文分析该院2018年3月收治的1例产前超声诊断骨骼畸形胎儿，通过基因检测检出胎儿为ACH，不排除合并AO1，通过文献学习，研究基因-表型关系，为临床遗传咨询提供指导。
1 资料与方法
1.1 资料来源
厦门大学附属第一医院2018年3月收治1例胎儿骨骼发育异常病例。
1.2 方法, 百拇医药(商梅娇 汪燕)