基于连锁分析的Ⅲ型短肋-多指综合征无创产前基因检测  

Noninvasive prenatal genetic testing for short-rib-polydactyly syndrome type Ⅲ based on linkage analysis

作　　者：李佳特[1] 吕远[1,2] 刘彩霞 尹少尉[1,2] 李闯 张志涛[1,2] LI Jia-te;LYU Yuan;LIU Cai-xia;YIN Shao-wei;LI Chuang;ZHANG Zhi-tao(Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院,辽宁沈阳110004 [2]辽宁省母胎医学重点实验室,辽宁本溪117004

出　　处：《中国实用妇科与产科杂志》2022年第8期834-838,共5页Chinese Journal of Practical Gynecology and Obstetrics

基　　金：国家自然科学基金(81701462)。

摘　　要：目的 探讨基于父母单体型的连锁分析,对1例Ⅲ型短肋-多指综合征家系进行无创产前基因检测。方法 2019年3月11日中国医科大学附属盛京医院收治的1例前期已诊断为短肋-多指综合征家系患者,致病位点明确,且已经通过靶向测序确认致病变异位点上下游1 Mb范围内的可用于连锁分析的单核苷酸多态性(single nucleotide polymorphisms,SNP)位点,利用SNP位点构建先证者与其父母的单体型。经充分交代与知情同意,孕9周时抽取再次妊娠时母亲外周血,分离血浆游离DNA,由构建的基因连锁图谱进行无创产前连锁分析,检测该次妊娠胎儿有无致病变异的携带情况。于孕12周对患者自然流产胎儿进行致病位点检测,验证无创产前基因检测结果。结果 通过对母源外周血中游离DNA连锁分析检测结果提示胎儿不携带父源致病位点,并且与流产组织检测结果一致。结论 基于连锁分析的无创产前基因检测准确地判断胎儿有无携带父源致病变异,具有临床意义。Objective To perform noninvasive prenatal genetic testing for a case of short rib-polydactyly syndrome typeⅢ based on linkage analysis of haplotypes.Methods The pathogenic sites in the family with short-rib-polydactyly syndrome type Ⅲ,who was admitted on March 11th,2019 in Shengjing Hospital of China Medical University,were clear,and the single nucleotide polymorphisms(SNPs)within 1 Mb upstream and downstream of the pathogenic sites were identified by targeted sequencing,which could be used for linkage analysis,and the haplotypes of the proband and their parents were constructed using the SNP sites. The peripheral blood was extracted from the pregnant woman(9 weeks of gestation)after informed consent,and the fetal free DNA was separated from plasma. Noninvasive prenatal linkage analysis was performed on the constructed gene linkage map to detect the carrying status of pathogenic variation in fetuses. Pathogenic sites were detected in aborted fetuses at 12 weeks of gestation to verify the results of noninvasive prenatal genetic testing.Results The results of fetal free DNA linkage analysis in maternal peripheral blood indicated that the fetus did not carry the paternal pathogenic site,which was consistent with the detection results of abortion tissue.Conclusion Noninvasive prenatal genetic testing based on linkage analysis can accurately determine paternal pathogenic variation in fetuses and has a promising clinical significance.

关 键 词：无创产前基因检测 连锁分析 Ⅲ型短肋-多指综合征 

分 类 号：R714.53[医药卫生—妇产科学]