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

TY - JOUR

T1 - 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

AU - Rydder, Pernille Marker

AU - Andreasen, Lotte

AU - Thomsen, Simon Horsholt

AU - Jensen, Uffe Birk

AU - Becher, Naja

AU - Dunø, Morten

AU - Vogel, Ida

N1 - Publisher Copyright: © 2025 The Authors

PY - 2025/5

Y1 - 2025/5

N2 - 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.

AB - 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.

KW - Array comparative genomic hybridization

KW - Chorionic villus sampling

KW - Chromosome fragile sites

KW - Mosaicism

KW - Placenta

KW - Prenatal diagnosis

UR - http://www.scopus.com/inward/record.url?scp=105000854080&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2025.03.016

DO - 10.1016/j.placenta.2025.03.016

M3 - Journal article

C2 - 40157041

AN - SCOPUS:105000854080

SN - 0143-4004

VL - 165

SP - 16

EP - 22

JO - Placenta

JF - Placenta

ER -