目的:通过联合染色体核型分析,确定胎儿镶嵌性小数字标记染色体(sSMC)的起源和含量,染色体微阵列分析(CMA)和荧光原位杂交(FISH)。
方法:选取2022年在深圳市龙华区妇幼保健院就诊的1名31岁孕妇的胎儿作为研究对象。无创性产前检测提示胎儿在4q12q13.1中存在8.75Mb重复。在知情同意的情况下,从这对夫妇身上采集羊水和外周血样本进行染色体核型分析。sSMC的来源和含量由CMA鉴定,用FISH测定法测定其在羊水中的比例。
结果:孕妇的核型,她的丈夫和胎儿分别被确定为46,XX,46,XY,inv(9)(p12q12),和47,XY,inv(9)(p12q12)pat,+mar[75]/46,XY,inv(9)(p12q12)pat[25]。羊水样本的CMA测试为arr[hg19]4p11q13.1(48978053_63145931)×3,未显示镶嵌性。然而,FISH分析表明,培养的羊水样品中59%的间期细胞含有4号染色体着丝粒的三个信号,而重新取样的羊水中65%的间期细胞具有三个这样的信号,这证实了三体8镶嵌的存在。
结论:染色体结构异常合并镶嵌可以通过联合染色体核型分析和分子技术如FISH和CMA来描述,这为家庭提供了更准确的咨询。
OBJECTIVE: To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH).
METHODS: The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay.
RESULTS: The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46,XX, 46,XY,inv(9)(p12q12), and 47,XY,inv(9)(p12q12)pat,+mar[75]/ 46,XY,inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism.
CONCLUSIONS: Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.