新发46,X,der(X)t(X;Y)(q26;q11)胎儿1例的遗传学分析

Genetic analysis of a fetus with de novo 46,X,der(X)t(X;Y)(q26;q11)

目的对1例新发46, X, der(X)t(X;Y)(q26;q11)胎儿进行产前遗传学分析。方法选取2021年5月22日就诊于连云港市妇幼保健院的1例孕妇作为研究对象。收集孕妇的临床资料, 采集夫妇的外周静脉血样以及胎儿的脐血样本, 进行常规的G显带核型分析。提取羊水DNA, 对其进行染色体微阵列分析(CMA), 并对变异的致病性进行分析。结果孕25周超声检查提示胎儿为永存左上腔静脉, 二、三尖瓣少量反流。G显带核型分析显示, 胎儿Y染色体pter-q11片段易位至X染色体长臂q26处, 孕妇夫妇核型均未见明显异常。CMA检测显示, 胎儿X染色体长臂末端存在约21 Mb的缺失[arr[hg19]Xq26.3q28(133912218154941869)×1], Y染色体长臂存在约42 Mb的重复[arr[hg19]Yq11.221qter(1740591859032809)×1]。结合DGV、OMIM、DECIPHER、ClinGen及PubMed等数据库的检索结果, 根据美国医学遗传学与基因组学学会(ACMG)相关指南, 判断上述Xq26.3q28缺失为致病性, Yq11.221qter重复为临床意义不明。结论 Xq-Yq相互易位可能是胎儿的遗传学病因, 预测可导致卵巢功能障碍与发育迟缓。联合应用G显带核型分析与CMA检测能够及时诊断胎儿染色体结构异常的类型与来源、区分平衡和不平衡易位, 对孕妇妊娠结局的选择具有重要的参考价值。

Objective To carry out prenatal genetic testing for a fetus with de novo 46,X,der(X)t(X;Y)(q26;q11).Methods A pregnant woman who had visited the Birth Health Clinic of Lianyungang Maternal and Child Health Care Hospital on May 22,2021 was selected as the study subject.Clinical data of the woman was collected.Peripheral blood samples of the woman and her husband and umbilical cord blood of the fetus were collected and subjected to conventional G-banded chromosomal karyotyping analysis.Fetal DNA was also extracted from amniotic fluid sample and subjected to chromosomal microarray analysis(CMA).Results For the pregnant women,ultrasonography at 25th gestational week had revealed permanent left superior vena cava and mild mitral and tricuspid regurgitation.G-banded karyotyping analysis showed that the pter-q11 segment of the fetal Y chromosome was connected to the Xq26 of the X chromosome,suggesting a Xq-Yq reciprocal translocation.No obvious chromosomal abnormality was found in the pregnant woman and her husband.The CMA results showed that there was approximately 21 Mb loss of heterozygosity at the end of the long arm of the fetal X chromosome[arr[hg19]Xq26.3q28(133912218_154941869)×1],and 42 Mb duplication at the end of the long arm of the Y chromosome[arr[hg19]Yq11.221qter(17405918_59032809)×1].Combined with the search results of DGV,OMIM,DECIPHER,ClinGen and PubMed databases,and based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the deletion of arr[hg19]Xq26.3q28(133912218_154941869)×1 region was rated as pathogenic,and the duplication of arr[hg19]Yq11.221qter(17405918_59032809)×1 region was rated as variant of uncertain significance.Conclusion The Xq-Yq reciprocal translocation probably underlay the ultrasonographic anomalies in this fetus,and may lead to premature ovarian insufficiency and developmental delay after birth.Combined G-banded karyotyping analysis and CMA can determine the type and origin of fetal chromosomal structural abnormalities as well as distinguish balanced and unbalanced translocations,which has important reference value for the ongoing pregnancy.