Abstract:

Objective: To explore the clinical significance of detecting Xp22.31 microdeletion/microduplication in prenatal diagnosis. Methods: A retrospective analysis was conducted on the data of 6 015 pregnant women who underwent the chromosome karyotype analysis and single nucleotide polymorphism array (SNP-array) testing of amniotic fluid/umbilical cord blood at the Prenatal Diagnosis Center of Quanzhou Women's and Children's Hospital from January 2017 to October 2023. The cases were grouped based on the confirmed Xp22.31 microdeletion/microduplication fetuses. The prenatal manifestations, genetic testing results, and follow-up outcomes were analyzed and compared between the two groups. Results: Among the 6 015 pregnant women, 68 cases of Xp22.31 microdeletion/microduplication were found by SNP-array. There were 18 cases of Xp22.31 microdeletion (13 males and 5 females). Five cases were verified by parents, of which 4 cases were inherited from their mothers with normal phenotype and 1 case was de novo mutation. Among 14 cases of Xp22.31 microdeletion with high risk of prenatal Down's syndrome screening(DSS), 11 cases had unconjugated estriol multiple of the median (uE₃MOM) values <0.1, which was significantly lower than the normal range. Among the 13 male microdeletion carriers, 1 terminated pregnancy, 1 lost follow-up, 11 continued pregnancy, 9 cases were diagnosed with ichthyosis after birth, and 2 had no obvious abnormalities. Five female deletion carriers were all born without obvious abnormalities. There were 50 cases of Xp22.31 microduplication (19 males and 31 females), 27 cases were verified by parents, and all of them were inherited from their parents. Of the 50 fetuses, 5 fetuses terminated pregnancy, 2 fetuses were lost to follow-up, and 43 fetuses continued pregnancy. Two fetuses had abnormal symptoms after birth, and the remaining 41 fetuses had no abnormalities. There were no significant differences in maternal age, ultrasound abnormality rate, and parental verification results between the two groups (all P>0.05). The high-risk rate of DSS and the proportion of male fetuses in the microdeletion group were higher than those in the microduplication group, while the detection rate and the rate of benign pregnancy outcomes in the microdeletion group were lower than those in the microduplication group (both P<0.05). The uE₃MOM value of high-risk fetuses in the DSS of the microdeletion group was lower than that of the microduplication group (P<0.05). Conclusions: Fetuses with Xp22.31 microdeletion/microduplication lack typical prenatal clinical features. For pregnant women with high risk of prenatal serological screening, especially those whose uE₃MOM value is significantly lower than the normal range, chromosomal microchange detection should be recommended. Male fetuses with Xp22.31 microdeletion mainly present with ichthyosis phenotype after birth, while female Xp22.31 microdeletion carriers have good pregnancy outcomes. Most of the Xp22.31 microduplication is parental inheritance, and the pregnancy outcome of fetus is likely to be benign.

Key words: Chromosomes, Prenatal diagnosis, Fetus, Ultrasonography, Genetic techniques, Polymorphism, single nucleotide, Microarray analysis, Xp22.31 microdeletions/microduplications