Prenatal diagnosis and molecular cytogenetic analysis of Xp22.31 microdeletions and microduplications in Chinese populations

Chromosome rearrangements are frequently observed in the Xp22.31 region. Xp22.31 microdeletion is linked to X-linked ichthyosis, whereas the pathogenicity of Xp22.31 microduplication remains a subject of controversy. In the present study, 52 additional foetuses with Xp22.31 microdeletions/microduplications were presented, with the aim of providing further insights into the prenatal diagnosis and genetic counselling of Xp22.31 microdeletions/microduplications. A retrospective analysis was conducted involving a total of 4,251 pregnant women who received amniocentesis of prenatal diagnosis in our hospital from January 2017 to August 2022. All of the subjects were subjected to karyotype and chromosomal microarray analysis (CMA) for evaluation of chromosomal abnormalities. Whole exome sequencing (WES) was subsequently employed to explore additional variants in individuals presenting unexplained clinical features. Among the enrolled subjects, a total of 52 cases with Xp22.31 microdeletions/microduplications were detected using CMA, with a detection rate of 1.22% (52/4251). A total of 35 foetuses carried Xp22.31 microduplications and most of them exhibited normal developmental milestone after birth, except one case with motor and speech developmental delay. Additionally, 17 foetuses harbored Xp22.31 microdeletions, 10 male foetuses exhibited ichthyosis after birth, 6 female foetuses manifested normal clinical features, and the remaining were terminated based on parental request. In the present study, WES was further conducted on a foetus with renal abnormalities; however, no likely pathogenic or pathogenic variants in genes related to the observed phenotype were identified. The present authors propose that Xp22.31 microduplication may be a benign copy number variant. In addition, the findings reveal, for the first time, a previously unknown association between renal agenesis and Xp22.31 microdeletion, thus expanding the range of clinical manifestations associated with Xp22.31 microdeletions.