苏华+陈琛+张斌

    [摘要] 目的 对超声检查疑为短肢畸形的胎儿进行致病基因成纤维细胞生长因子受体3(FGFR3)全外显子突变分析产前基因诊断及遗传咨询。 方法 从UCSC Genome Bioinformatics数据库中提取包括FGFR3基因全部17個外显子的2个转录本的相关序列作为标准序列，设计合成FGFR3全基因外显子扩增的共8对引物。收集2014年1月～2016年12月在河北北方学院附属第一医院就诊的5例疑为短肢畸形的胎儿，对高危胎儿于B超引导下行羊水穿刺，富集细胞，对FGFR3基因外显子组进行PCR扩增，应用Sanger基因测序技术进行FGFR3基因全外显子测序，采用CodonCode Aligner软件对测序结果进行错义突变位点分析，判断其是否存在致病突变。 结果 5例疑为短肢畸形的胎儿，其中1例胎儿FGFR3基因(转录本NM_000142.4)第7号外显子(FGFR3-7-IS1)携带错义突变C.1138G>A(P.Arg380Gly)，其余4例未发现FGFR3基因突变。对明确了致病突变的5例孕早期胎儿家属进行遗传咨询。 结论 对疑似短肢畸形胎儿应用基因测序技术进行产前FGFR3基因突变的检测可以预防短肢畸形患儿的出生。

    [关键词] 短肢畸形；软骨发育不全；成纤维细胞生长因子受体3；突变；产前诊断

    [中图分类号] R714.53 [文献标识码] A [文章编号] 1673-7210(2017)12(b)-0016-04

    [Abstract] Objective To identify the fibroblast growth factor receptor 3 (FGFR3) mutation of fetuses with short limbs deformity and carry out genetic counseling by fetuses found in ultrasound screening. Methods The genomic information of FGFR3 full 17 exon amplification from UCSC Genome Bioinformatics， including 2 genome transcripts were extracted as a standard sequence， 8 pairs of primers were designed. 5 fetuses suspected to be with short limb deformities in the First Affiliated Hospital of Hebei North University from January 2014 to December 2016 were selected and the amniotic fluid of the fetuses in high-risk was collected for detection of mutation of FGFR3 gene by polymerase chain reaction and Sanger gene sequencing. The mutation of the sequencing of FGFR3 gene was carried out by CodonCode Aligner software. Results Among the 5 fetuses with short limbs deformity ......