Authors: Rajcan-Separovic, E.; Diego-Alvarez, D.; Robinson, W.P.; Tyson, C.; Qiao, Y.; Harvard, C.; Fawcett, C.; Kalousek, D.; Philipp, T.; Somerville, M.J.; Stephenson, M.D.

Source: Human Reproduction, Volume 25, Number 11, 16 November 2010 , pp. 2913-2922(10)

Publisher: Oxford University Press

Abstract:

BACKGROUND

Recurrent pregnancy loss (RPL), defined as two or more miscarriages, affects 35 of couples trying to establish a family. Despite extensive evaluation, no factor is identified in 40 of cases. In this study, we investigated the possibility that submicroscopic chromosomal changes, not detectable by conventional cytogenetic analysis, exist in miscarriages with normal karyotypes (46,XY or 46,XX) from couples with idiopathic RPL.

METHODS

Array comparative genomic hybridization (array-CGH) was used to assess for DNA copy number variants (CNVs) in 26 miscarriages with normal karyotypes. Parental array-CGH analysis was performed to determine if miscarriage CNVs were de novo or inherited.

RESULTS

There were 11 unique (previously not described) CNVs, all inherited, identified in 13 miscarriages from 8 couples. The maternal origin of two CNVs was of interest as they involved the imprinted genes TIMP2 and CTNNA3, which are only normally expressed from the maternal copy in the placenta. Two additional cohorts, consisting of 282 women with recurrent miscarriage (RM) and 61 fertile women, were screened for these two CNVs using a Quantitative Multiplex Fluorescent PCR of Short Fragments assay. One woman with RM, but none of the fertile women, carried the CTNNA3-associated CNV.

CONCLUSIONS

This preliminary study shows that array-CGH is useful for detecting CNVs in cases of RPL. Further investigations of CNVs, particularly those involving genes that are imprinted in placenta, in women with RPL could be worthwhile.

Keywords: recurrent pregnancy loss; copy number variants (CNVs); miscarriage; TIMP2; CTNNA3

Document Type: Research article

DOI: http://dx.doi.org/10.1093/humrep/deq202

Publication date: 2010-11-16

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• Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.

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• In this Subject: Anatomy & Physiology ,  Obstetrics & Gynecology
• By this author: Rajcan-Separovic, E. ;  Diego-Alvarez, D. ;  Robinson, W.P. ;  Tyson, C. ;  Qiao, Y. ;  Harvard, C. ;  Fawcett, C. ;  Kalousek, D. ;  Philipp, T. ;  Somerville, M.J. ;  Stephenson, M.D.

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