Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion.
BACKGROUND
The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of recurrent spontaneous abortion (RSA) but the results obtained were conflicting.


OBJECTIVE
We therefore investigated the XCI patterns in peripheral blood DNA obtained from 80 patients who had RSA and 160 age-matched controls.


METHODS
Pregnancy history, age, karyotype, and disease information was collected from all subjects. The methylation status of a highly polymorphic cytosine-adenine-guanine repeat in the androgen-receptor (AR) gene was determined by use of methylation-sensitive restriction enzyme HpaII and polymerase chain reaction.


RESULTS
Skewed XCI (> 85% skewing) was observed in 13 of the 62 patients informative for the AR polymorphism (20.9%), and eight of the 124 informative controls (6.4%) (P = 0.0069; chi2 test). More importantly, extremely skewed XCI, defined as > 90% inactivation of one allele, was present in 11 (17.7%) patients, and in only two controls (P = 0.0002; chi2 test).


CONCLUSIONS
These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.
Bagislar
Sevgi
S
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Turkey.
Ustuner
Isik
I
Cengiz
Bora
B
Soylemez
Feride
F
Akyerli
Cemaliye Boylu
CB
Ceylaner
Serdar
S
Ceylaner
Gulay
G
Acar
Aynur
A
Ozcelik
Tayfun
T
D000026:Abortion, Habitual / Q000235:genetics*; D000483:Alleles; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D005260:Female; D006801:Humans; D009030:Mosaicism; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics*; D049951:X Chromosome Inactivation
D011944:Receptors, Androgen; D004247:DNA