基于NGS技术的FGFR3基因突变胎儿产前临床表型与基因型分析  

The analysis of prenatal clinical phenotype and genotype among FGFR3 mutation fetuses based on NGS technology

作　　者：黄演林[1] 石晓梅[1] 汪安石[1] 刘畅[1] 余丽华[1] 黄翠青 张彦[1] Huang Yanlin;Shi Xiaomei;Wang Anshi;Liu Chang;Yu Lihua;Huang Cuiqing;Zhang Yan(Guangdong Women and Children Hospital,Guangzhou 510010,Guangdong,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511400 [2]广东省妇幼保健院超声科,广东广州511400

出　　处：《中国产前诊断杂志（电子版）》2022年第2期30-35,共6页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：广东省医学科学技术研究基金项目(A2020302);广东省医学科学技术研究基金项目(B2021258)。

摘　　要：目的对产前超声提示骨骼发育异常的家系进行高通量测序[又称二代测序(next-generation sequencing,NGS)],对确诊为FGFR3基因致病突变的胎儿进行产前临床表型和基因型分析,为产前诊断和遗传咨询提供依据。方法收集2018年10月至2020年12月于产前超声提示骨骼发育异常的胎儿进行羊水或脐血穿刺,同时收集父母的外周血,进行全外显子组或医学外显子组检测,对确诊为FGFR3致病突变的胎儿行产前临床表型与基因型分析,所有产前标本均进行母血污染鉴定和阳性位点行Sanger测序验证。结果在11个家系中发现FGFR3基因致病突变的胎儿,胎儿四肢长骨呈不同程度偏小(2~12周),一般随孕周增加而加重,3例(27.3%)胎儿双顶径及头围偏大。NGS结果显示,11例胎儿均为FGFR3错义变异致病,包含4种不同的致病位点。其中8例为c.1138G>A(8/11,72.7%),诊断为胎儿软骨发育不全;c.1118A>G和c.742C>T各1例,诊断为胎儿致死性软骨发育不全1型;1例为c.1620C>A,诊断为软骨发育不全/软骨发育不良。全部位点均为新发杂合变异,所有胎儿均被引产。结论NGS技术对FGFR3基因突变引起的骨骼异常具有较大的产前诊断价值,进一步明确该类病的产前临床表型和基因型特点,为产前诊断和遗传咨询提供依据。Objective To perform high-throughput sequencing[next-generation sequencing(NGS)]for families with skeletal dysplasia revealed by prenatal ultrasound,and to analyze prenatal clinical phenotype and genotype among fetuses diagnosed with FGFR3pathogenic variants.Methods From October 2018to December 2020,the amniotic fluid or cord blood was collected from fetuses with skeletal dysplasia indicated by prenatal ultrasound.All prenatal specimens and the peripheral blood of their parents were detected by whole exome or medical exome sequencing.Identification of maternal blood contamination must be done before tests and positive sites were verified by Sanger sequencing.Results The fetuses with FGFR3 pathogenic variants were found in 11 families.The long bones of the fetal limbs were variably shorter than the average,and generally aggravated with the increasing of gestational age.Biparietal diameters and head circumference were too big in 3 cases(27.3%)of the fetuses;NGS results show that 11 cases of fetuses are all caused by FGFR3missense variants,including 4 different pathogenic sites,of which 8 cases are c.1138G>A(8/11,72.7%),and the diagnosis is fetal achondroplasia,1 case each of c.1118A>G and c.742C>T,was diagnosed as fetal lethal achondroplasia type 1,and 1case was c.1620C>A,which was diagnosed as achondroplasia/chondroplasia.All loci were de novo heterozygous variants,and all fetuses chose induced abortion.Conclusion NGS technology is of great value in prenatal diagnosis of skeletal abnormalities caused by FGFR3 mutation.Clarification of the prenatal phenotype and genotype characteristics of the disease could facilitate the prenatal diagnosis and genetic counseling.

关 键 词：高通量测序 FGFR3基因 软骨发育不全 产前诊断 

分 类 号：R714.55[医药卫生—妇产科学]