Mosaic STS gene deletions in chorionic villus samples are often confined to the placenta, and they differ in size from STS gene deletions in patients with X-linked Ichthyosis

Abstract

Objective

This study presents several cases of mosaicism for STS gene deletions in uncultured chorionic villus samples analyzed with chromosomal microarray without prior trypsinization. We aimed to confirm these results with MLPA on the chorionic villus samples and to evaluate the presence of mosaicism in follow-up amniocentesis.

Methods

We retrospectively collected cases of prenatally identified STS gene deletions in chorionic villus samples and amniocenteses at Aarhus University Hospital. A subgroup with mosaic microarray results was analyzed with MLPA.

Results

Four non-mosaic (of which three were inherited) and 16 mosaic STS gene deletions were identified. Mosaicism was confirmed with MLPA in all cases suitable for MLPA analysis. All 10 mosaic cases with follow-up amniocentesis showed normal results. In general, STS gene deletions in a mosaic state were smaller in size and had breakpoints located within the common fragile site FRAXB, whereas non-mosaic STS deletions were larger with breakpoints located close to VCX genes. Deletion size differed significantly between mosaic cases of this study and STS gene deletions in patients with X-linked Ichthyosis reported in ClinVar.

Conclusion

We report and confirm several cases of placental mosaicism for STS gene deletions. All mosaic cases with follow-up amniocentesis were confined to the placenta. Mosaic deletions likely arose from strand breaks at the common fragile site FRAXB, whereas the classical non-mosaic genotype found in patients with X-linked Ichthyosis arises from non-allelic homologous recombination during meiosis. These results support the existing hypothesis that placental mosaicism for copy number variants likely arise in common fragile sites.