Analysis of X chromosome inactivation and prenatal diagnosis for a Chinese pedigree with loss of heterozygosity at Xq22.1q22.3
10.3760/cma.j.cn511374-20221224-00889
- VernacularTitle: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
- Author:
Xuejun CHEN
1
;
Weiguo ZHANG
Author Information
1. 台州医院生殖中心，台州 317000
- Keywords:
Prenatal diagnosis;
Loss of heterozygosity at Xq22.1q22.3;
X chromosome inactivation;
Genotype;
Clinical phenotype
- From:
Chinese Journal of Medical Genetics
2024;41(3):326-330
- CountryChina
- Language:Chinese
-
Abstract:
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.
