Center of Prenatal Diagnosis, Zhanjiang Maternity and Child Health Care Hospital, Zhanjiang, China.
Guangzhou Jingke Biotechnology Co., Ltd, Guangzhou, P. R. China.
BMC Med Genomics. 2024 Feb 21;17(1):57. doi: 10.1186/s12920-024-01824-8.
Copy number variation (CNV) of X chromosome can lead to a variety of neonatal abnormalities, especially for male fetuses. In recent years, due to the high sensitivity and high specificity of NIPS, its application has gradually expanded from chromosome aneuploidy to CNV. Few prenatal cases involving the detection of Xq duplication and deletion by NIPS have been reported, but it is of great significance for genetic counseling.
A 36-year-old woman was referred for prenatal diagnosis and genetic counseling at 17 weeks of gestation because of abnormal result of noninvasive prenatal screening (NIPS). Multiple congenital malformations, hydrocephalus, and enlarged gallbladder were observed by prenatal ultrasound. Amniocentesis revealed the karyotype of the fetus as 46, XN, add(X) (p22.2) and the result of chromosomal microarray analysis was arr[hg19] Xq27.1q28(138,506,454-154896094) × 2 and arr[hg19] Xp22.33p22.32(168,551-5,616,964) × 1. CNV-seq showed that the mother shares a 16.42 Mb duplication in the Xq27.1-q28 region and a 2.97 Mb deletion in the Xp22.33-p22.32 region. After genetic counseling, the couple chose to terminate the pregnancy.
The combination of NIPS and CMA would be of values in detection of subchromosomal duplications and/or deletions at fetal stage. The detection of X chromosome aberration in a male fetus should give suspicion of the possibility of maternal inheritance.
X 染色体的拷贝数变异 (CNV) 可导致多种新生儿畸形，尤其是男性胎儿。近年来，由于 NIPS 具有较高的灵敏度和特异性，其应用已逐渐从染色体非整倍体扩展到 CNV。虽然已有少数产前病例通过 NIPS 检测到 Xq 重复和缺失，但这对于遗传咨询具有重要意义。
一名 36 岁女性因无创产前筛查（NIPS）异常结果而在 17 孕周时被转诊行产前诊断和遗传咨询。产前超声检查发现胎儿存在多种先天性畸形、脑积水和胆囊增大。羊膜穿刺术显示胎儿核型为 46,XN,add(X)(p22.2)，染色体微阵列分析结果为 arr[hg19]Xq27.1q28(138,506,454-154896094)×2 和 arr[hg19]Xp22.33p22.32(168,551-5,616,964)×1。CNV-seq 显示母亲在 Xq27.1-q28 区域共享 16.42Mb 重复，在 Xp22.33-p22.32 区域共享 2.97Mb 缺失。遗传咨询后，夫妇选择终止妊娠。
NIPS 和 CMA 的结合可用于检测胎儿亚染色体的重复和/或缺失。男性胎儿 X 染色体异常应怀疑母体遗传的可能性。
