产前母源性UPD(16)的临床病例随访及遗传学分析  

Clinical and genetic analysis of a case of prenatal maternal UPD(16)

作　　者：曾果 林彭思远 卜秀芬 周世豪 曾黎 Zeng Guo;Lin Pengsiyuan;Bu Xiufen;Zhou Shihao;Zeng Li(Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control,Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University,Changsha 410007,Hunan,China)

机构地区：[1]湖南师范大学附属长沙市妇幼保健院,区域遗传性出生缺陷防控研究湖南省重点实验室,湖南长沙410007

出　　处：《中国产前诊断杂志（电子版）》2024年第1期16-21,共6页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：湖南省胎儿先心病遗传研究临床医疗技术示范基地基金资助项目(2021SK4036)。

摘　　要：目的对1例产前超声诊断为宫内生长受限的胎儿进行遗传学分析及出生后随访。方法孕24^(+)周孕妇因孕中期血清学筛查21三体高风险、扩展性无创产前检测提示16号染色体数目偏多和胎儿生长受限行介入性产前诊断,取胎儿羊水细胞行染色体核型分析、染色体微阵列分析(chromosomal microarray analysis,CMA)和全外显子组测序(whole exome sequencing,WES)分析。抽取父母静脉血,提取基因组DNA,分析确定胎儿变异的遗传来源。结果320条带G显带核型分析未见异常,全外显子组测序结果未检出与受检者临床表型相关的致病/疑似致病变异/遗传模式相符的临床意义未明变异。CMA未检出有临床意义的拷贝数变异,但提示:arr[hg19]16p13.3p12.2(94,808-23,024,688)x2 hmz,即胎儿16号染色体16p13.3p12.2区域存在22.93Mb的纯合区域。经过对父母和胎儿的SNP位点进行比对分析,确定这1例胎儿为整条16号染色体的混合型母源性单亲二体。充分告知遗传学风险后,父母决定继续妊娠。新生儿出生时体重极低,但出生后生长追赶,精神运动发育良好,目前已随访至2岁6月。结论本病例存在的母源性16号染色体单亲二体和胎儿生长受限表型可能没有直接关联,本研究中胎儿FGR的致病原因可能是由胎盘16号染色体三体造成,这为今后产前母源性UPD(16)的遗传咨询提供了参考。Objective To analyze the genetics of a fetus with fetal growth restriction(FGR)diagnosed by prenatal ultrasonography and followed up after birth.MethodsA healthy woman underwent amniocentesis at 24 weeks of gestation because of a high risk of Down syndrome,high risk of expanded non-invasive prenatal testing for trisomy 16 and FGR.Amniocentesis followed by karyotype,chromosomal microarray analysis(CMA)and whole exome sequencing(WES)were performed.Results The fetus had a normal karyotype,no apparent copy number variation and genovariation.22.93Mb of homozygous copy-neutral regions on chromosome 16pl3.3pl2.2 were identified,which showed that the fetus carried the whole maternal UPD(16)with segmental hetero-and isodisomy.The parents decided to continue with the pregnancy after genetic counseling,and the neonate was born with very low birth weight and catch-up growth after birth during a long-term intensive follow-up.Conclusion In this case,there may be no direct correlation between maternal UPD(16)and FGR.FGR phenotype of the proband may result from the trisomy 16 in placenta.Our study present a reference for the prenatal diagnosis and genetic counseling of UPD(16)in the future.

关 键 词：产前诊断 单亲二体 胎儿生长受限 无创产前检测 

分 类 号：R715.5[医药卫生—妇产科学]