软骨发育不全家系FGFR3基因突变检测和产前诊断  

Analysis of FGFR3 mutations in achondroplasia patients and prenatal diagnosis

作　　者：李焕铮 项延包 吴洁丽 董雪琴 徐雪琴 唐少华 LI Huan-zheng XIANG Yan- bao WU Jie-li DONG Xue-qin XU Xue-qin TANG Shao-hua.(Wenzhou Central Hospital, Wenzhou 325000, Chin)

机构地区：[1]温州市中心医院,浙江温州325000

出　　处：《中国优生与遗传杂志》2017年第1期26-28,19,共4页Chinese Journal of Birth Health & Heredity

基　　金：浙江省人口计生委项目(JSW2012-B003);温州市科技计划项目(Y20120138)

摘　　要：目的应用Sanger恻序对软骨发育不全(Achondroplasia,ACH)家系患者进行FGFR3基因c.1138G>A突变检测,建立ACH的基因诊断方案,为ACH家系进行产前诊断及遗传咨询提供有价值的资料。方法收集5个疑似ACH家系的先证者及其父母外周血,提取DNA,采用Sanger测序技术进行FGFR3基因c.1138G>A检测;对ACH高危孕妇进行绒毛、羊水穿刺,进行产前基因诊断;所有绒毛或羊水标本均进行母血污染鉴定。结果 1个曾生育ACH患儿家系,父母基因型正常,绒毛检测结果显示未见异常;2个父源性FGFR3基因c.1138G>A突变家系,羊水穿刺结果显示胎儿为FGFR3基因c.1138G>A突变,超声结果提示四肢短小、胸廓狭窄,为软骨发育不全患者;1个母源性FGFR3基因c.1138G>A突变家系,超声提示胎儿四肢短小,疑似软骨发育不全患者,脐血检测结果胎儿基因型为c.1138G>A突变,选择引产,3个月后再次妊娠,早期绒毛检测,胎儿为c.1138G>A突变,早期超声未见异常,自行继续妊娠,中晚期超声提示胎儿股骨偏小4周,决定引产;1个母源性FGFR3基因c.1138G>A突变家系,绒毛检测胎儿基因型未见异常;2例基因型正常胎儿,孕期超声检查未发现异常,随访至出生后1年,表型正常,均为健康个体。结论建立FGFR3基因c.1138G>A位点诊断体系,可为ACH患者和有检测需求的人群提供技术手段和遗传咨询依据,预防出生缺陷的发生。Objective： In this paper, we examined the achondroplasia （ACH） patients with special mutation site c.1138G〉A in the fibroblast growth factor receptor-3 gene （FGFR3） by sanger sequencing. So it can provide a valuable approach for detecting the most common FGFR3 mutations carried by patients with ACH. Methods 5 ACH families were collected from Wenzhou Prenatal Diagnosis Center. Methods： The samples were detected with mutations in nucleotide 1138 （Gly380Arg） of FGFR3 by direct sequencing. We collected all the prenatal diagnosis samples from women carrying fetus at risk of ACH. Identification of maternal blood contamination must be done before tests. Results： One case with ACH childbearing history was fully evaluated. No mutation was found in chorionic villi. In two families, the fathers were ACH patients and carry the common G1138 （G380R） mutation in the FGFR3 gene. The fetus was found to carry c. 1138G 〉A mutations of FGFR3 by amniocentesis. Detailed fetal ultrasound studies showed a short limbs, and a small chest, these changes indicated the fetus were ACH. In another case, the mother is ACH due to the common c. 1138G 〉A mutation in FGFR3 gene, while the father has normal phenotype. Neither had genetic counseling or molecular testing prior to the pregnancy. Antenatal ultrasound study at 28 weeks of gestation showed short femur was noted in fetus with FL less than 4SD. Fetal genetic diagnosis using umbilical cord blood was conducted to determine the c. 1138G 〉A mutation of FGFR3 gene. We found it has the same mutation with its mother. After 3 months, she was pregnant again. Fetal genetic diagnosis of chorionic villi has the same mutation again. For early ultrasound was normal, so this pregnant woman decided to continue the pregnancy. Her fetus demonstrated abnormally short femur at 23 and 28week＇ s gestation by ultrasound scan, and was highly suspected with dwarfism. So she decided to induce labor. In the last family, the mother is also ACH patient, no mutation was found in chorioni

关 键 词：软骨发育不全 FGFR3 产前诊断 

分 类 号：R440[医药卫生—诊断学] R681.1[医药卫生—临床医学]