Analysis of X chromosome inactivation and prenatal diagnosis for a Chinese pedigree with loss of heterozygosity at Xq22.1q22.3
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
万方数据
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 Hpa Ⅱ. 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.
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 Hpa Ⅱ. 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.
Prenatal diagnosisLoss of heterozygosity at Xq22.1q22.3X chromosome inactivationGenotypeClinical phenotype
万方数据
