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Published on: July 18, 2025
Sex chromosome characteristics and recurrent miscarriage
Milja Kaare1, Jodie N Painter, Veli-Matti Ulander
1Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland. milja.kaare@helsinki.fi
Objective:
To investigate whether skewed X chromosome inactivation (XCI) and Y chromosome microdeletions are associated with recurrent miscarrige (RM).
Design:
A retrospective study.
Setting:
University hospital and genetic laboratory.
Patient(S):
Altogether, 46 women with a history of RM, defined as at least three miscarriages, and a control group of 95 women with no history of miscarriage were included in the XCI study. In the Y chromosome microdeletion study 40 male partners of women with RM were studied.
Intervention(S):
Blood samples for DNA extraction.
Main Outcome Measure(S):
X chromosome inactivation patterns in the females were analyzed using a methylation-sensitive assay. The DNA from males was tested for Y chromosome microdeletions by analyzing 37 sequence tagged sites.
Results:
Mildly skewed XCI (>85% inactivation of one allele) was detected in 4 of 43 (9.3%) patients, and 9 of 81 (11.1%) controls. Among these women, extremely skewed XCI (>90% inactivation of one allele) was detected in 2 of 43 (4.7%) patients, and 4 of 81 (4.9%) controls. No statistical differences could be shown between the groups. No microdeletions were found in the male partners.
Conclusion(S):
The frequency of both extremely and mildly skewed XCI was similar in patients and control women. Y chromosome microdeletions were not found in spouses of patients. Based on these results we conclude that skewed X inactivation and Y chromosome microdeletions are not associated with RM in our study couples.
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