Sex chromosome characteristics and recurrent miscarriage

Kaare, Milja; Painter, Jodie N.; Ulander, Veli-Matti; Kaaja, Risto; Aittomäki, Kristiina

doi:10.1016/j.fertnstert.2007.10.048

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Volume 90, Issue 6 , Pages 2328-2333, December 2008

Sex chromosome characteristics and recurrent miscarriage

Milja Kaare, M.Sc.
- Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland
- Reprint requests: Milja Kaare, M.Sc., Folkhälsan Institute of Genetics, Biomedicum Helsinki, P.O. Box 63, University of Helsinki, FIN-00014, Helsinki, Finland (FAX: +358 919125073).
Jodie N. Painter, Ph.D.
- Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland
Veli-Matti Ulander, M.D., Ph.D.
- Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Risto Kaaja, M.D., Ph.D.
- Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Kristiina Aittomäki, M.D., Ph.D.
- Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland
- Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland

Received 18 June 2007; received in revised form 26 October 2007; accepted 26 October 2007. published online 13 February 2008.

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.

Key Words: Recurrent miscarriage, Y chromosome, microdeletions, X chromosome inactivation