Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion
Author(s)
Date
2006Source Title
Australian and New Zealand Journal of Obstetrics and Gynaecology
Print ISSN
0004-8666
Publisher
Wiley-Blackwell Publishing Asia
Volume
46
Issue
5
Pages
384 - 387
Language
English
Type
ArticleItem Usage Stats
262
views
views
286
downloads
downloads
Abstract
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. Aims: 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 (> 8 5% 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; χ 2 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; χ 2 test). Conclusions: These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.
Keywords
Androgen receptorMosaicism
Mutation
Recurrent abortion
X-chromosome inactivation
Androgen receptor
DNA
Adult
Allele
Article
Controlled study
Female
Gene mutation
Genetic analysis
Genetic polymorphism
Genetic susceptibility
Human
Karyotype
Major clinical study
Pathogenesis
Polymerase chain reaction
Priority journal
Protein methylation
Receptor gene
Recurrent abortion
Risk factor
Sex chromosome mosaicism
Spontaneous abortion
Statistical analysis
Trinucleotide repeat
X chromosome inactivation
Abortion, Habitual
Alleles
DNA
DNA Methylation
Humans
Mosaicism
Polymorphism, Genetic
Pregnancy
Receptors, Androgen
X Chromosome Inactivation
Permalink
http://hdl.handle.net/11693/23708Published Version (Please cite this version)
http://dx.doi.org/10.1111/j.1479-828X.2006.00622.xCollections
Related items
Showing items related by title, author, creator and subject.
-
De novo balanced (X;14) translocation in a patient with recurrent miscarriages: Case report
Alpaslan Pinarli F.; Ökten G.; ÖzçelIk, T.; Kara, N.; Güneş, S.; Koçak I. (2011)We report a 23-year-old phenotypically normal female patient who had previously suffered from recurrent spontaneous abortion (RSA) who found to have an X;14 trans location and a Methylene- Tetrahdrofolate-Reductase (MTHFR) ... -
X chromosome inactivation and female predisposition to autoimmunity
Ozcelik, T. (Springer New York, 2008)[No abstract available] -
Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene
Kaplan, Y.; Vargel, I.; Kansu, T.; Akin, B.; Rohmann, E.; Kamaci, S.; Uz, E.; Ozcelik, T.; Wollnik, B.; Akarsu, N. A. (BMJ Group, 2008)Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions ...