Xq22.1q22.3杂合性缺失一个家系的X染色体失活分析及产前诊断  

Analysis of X chromosome inactivation and prenatal diagnosis for a Chinese pedigree with loss of heterozygosity at Xq22.1q22.3

作　　者：陈雪君 章卫国 Chen Xuejun;Zhang Weiguo(Reproductive Center of Taizhou Hospital,Taizhou,Zhejiang 317000,China;Central Laboratory of Taizhou Hospital,Taizhou,Zhejiang 317000,China)

机构地区：[1]台州医院生殖中心,台州317000 [2]台州医院中心实验室,台州317000

出　　处：《中华医学遗传学杂志》2024年第3期326-330,共5页Chinese Journal of Medical Genetics

基　　金：浙江省医药卫生科技计划(2021ky1196);台州恩泽医疗中心(集团)科研基金(21EZD46)。

摘　　要：目的分析1个Xq22.1q22.3杂合性缺失家系中女性X染色体失活(XCI)偏倚及逃逸情况与表型的相关性。方法回顾性分析2021年11月10日于台州医院确诊的1个Xq22.1q22.3杂合性缺失家系的临床资料。对该家系胎儿羊水以及孕妇夫妇的外周血样进行G显带染色体分析和拷贝数变异测序(CNV-seq),结合甲基化敏感性限制性核酸内切酶HpaⅡ消化前后PCR扩增雄性激素受体基因第1外显子CAG重复序列多态性的方法检测XCI。结果孕妇与胎儿的G显带核型均为46,X,del(X)(q22),CNV-seq检测结果均为seq[hg19]del(X)(q22.1q22.3)chrX:g.100460000_105740000del,提示X染色体q22.1q22区存在5.28 Mb的拷贝数缺失,孕妇丈夫未见明显异常。XCI分析提示孕妇与胎儿的X染色体的活性比均为0∶100,携带Xq22.1q22.3缺失的X染色体完全失活,胎儿的失活染色体源自母亲。结论胎儿携带母源性失活的X染色体del(X)(q22),携带者的表型与异常的X染色体活性密切相关。通过家系XCI分析结合孕妇临床表型有助于预测Xq22.1q22.3杂合性缺失家系女性胎儿的临床表型及预后,为遗传咨询提供依据。Objective To explore the correlation between skewed X chromosome inactivation(XCI)and clinical phenotype of a Chinese pedigree with loss of heterozygosity at Xq22.1q22.3.Methods A pedigree diagnosed at Taizhou Hospital on November 10,2021 was selected as the study subject.G-banded chromosomal karyotyping and copy number variation sequencing(CNV-seq)were carried out to analyze the amniotic fluid and peripheral blood samples from the couple.XCI was detected by PCR amplification of CAG repeats in exon 1 of androgen receptor gene before and after the digestion with methylation-sensitive restriction enzyme HpaⅡ.Correlation between the genotype and clinical phenotype was analyzed.Results The karyotypes of the pregnant woman and the fetus were both determined as 46,X,del(X)(q22),and the result of CNV-seq was seq[hg19]del(X)(q22.1q22.3)chrX:g.10046000_105740000del,suggesting that both had harbored a 5.28 Mb deletion on the X chromosome.No obvious abnormality was found in the husband.XCI analysis showed that the activity ratio of the two X chromosomes of the pregnant woman and her fetus was 0:100.The X chromosome harboring the q22.1q22.3 deletion was completely inactivated,and the inactivated X chromosome of the fetus was derived from its mother.Conclusion The fetus has harbored a maternally derived inactivated X chromosome del(X)(q22),and its phenotype is closely associated with the activity of the abnormal X chromosome.Pedigree XCI analysis combined with the clinical phenotype has facilitated recognition of the maternal phenotype and prognosis of female fetus with loss of heterozygosity at Xq22.1q22.3.

关 键 词：产前诊断 Xq22.1q22.3杂合性缺失 X染色体失活 基因型 临床表型 

分 类 号：R714.5[医药卫生—妇产科学]