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Novel missense mutation in WNT6 in 100 couples with unexplained recurrent miscarriage.

Authors :
Zhang Y
Li G
Fan Y
Cui Y
Huang S
Ma J
Yan J
Chen ZJ
Source :
Human reproduction (Oxford, England) [Hum Reprod] 2015 Apr; Vol. 30 (4), pp. 994-9. Date of Electronic Publication: 2015 Mar 06.
Publication Year :
2015

Abstract

Study Question: Do mutations and/or polymorphisms in coding sequences in Wingless-Type MMTV Integration Site Family, Member 6 (WNT6) play a role in unexplained recurrent miscarriage (unexplained RM) in Chinese couples?<br />Summary Answer: We found four mutations in the coding sequences of WNT6 which appear to exist in a small proportion of Chinese women with unexplained RM.<br />What Is Known Already: WNT6 has been proved to be essential for stromal cell proliferation during decidualization in mice, but in humans WNT6 has not been studied in recurrent miscarriage populations.<br />Study Design, Size, Duration: For this study, 100 couples with unexplained RM (at least three or more unexplained spontaneous miscarriages), and 100 ethnically matched fertile couples (at least one live birth and no history of pregnancy pathologies) were recruited. All the participants were chosen over a 7-year period from the National Research Center for Assisted Reproductive Technology and Reproductive Genetics at Shandong University, Jinan, China.<br />Participants/materials, Setting, Methods: Patients were recruited following extensive clinical studies. Genomic DNA was isolated from peripheral blood. Mutation analysis in the coding regions of WNT6 was performed by PCR amplification and DNA sequences testing in all participants. Functional effects of missense variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).<br />Main Results and the Role of Chance: Four rare novel mutations, including one missense mutation, were found in intron 1, exon 3 and the 3' untranslated region of WNT6 in four women with unexplained RM. Gene software predictions showed that the missense mutation in exon 3 could alter the function of WNT6. No mutations or polymorphisms were detected in the male partners of the unexplained RM patients or in the fertile controls. To further validate the findings, we continued to screen this missense mutation site in another 100 peripheral blood samples of normal fertile females, and there was still no positive result.<br />Limitations, Reasons for Caution: There is no direct evidence to validate whether these novel mutations discovered in the present research are related to unexplained RM. Further studies are warranted to investigate the role of WNT6 in unexplained RM, including larger studies in an independent group.<br />Wider Implications of the Findings: These results provide evidence to suggest the importance of WNT6 in reproductive failure and may support the hypothesis that WNT6 is essential for stromal cell proliferation during decidualization.<br />Study Funding/competing Interests: This work was supported by Science and Technology Development Planning of Shandong (2013GGE27001), the National Natural Science Foundation of China (81300459), the Science Projection of Bureau of Public Health in Weifang (2012044) and the Science Research Foundation Item of No-earnings Health Vocation. The authors have no competing interests to declare.<br /> (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1460-2350
Volume :
30
Issue :
4
Database :
MEDLINE
Journal :
Human reproduction (Oxford, England)
Publication Type :
Academic Journal
Accession number :
25750203
Full Text :
https://doi.org/10.1093/humrep/dev028