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Mol Cytogenet. 2015 Jan 31;8:6. doi: 10.1186/s13039-015-0109-8. eCollection 2015.

Functional consequences of copy number variants in miscarriage.

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Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5 Canada.
Child & Family Research Institute, Vancouver, V5Z 4H4 Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3 Canada.
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, V6Z 2 K5 Canada.
Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, 60612 USA.
Contributed equally



The presence of unique copy number variations (CNVs) in miscarriages suggests that their integral genes have a role in maintaining early pregnancy. In our previous work, we identified 19 unique CNVs in ~40% of studied euploid miscarriages, which were predominantly familial in origin. In our current work, we assessed their relevance to miscarriage by expression analysis of 14 genes integral to CNVs in available miscarriage chorionic villi. As familial CNVs could cause miscarriage due to imprinting effect, we investigated the allelic expression of one of the genes (TIMP2) previously suggested to be maternally expressed in placenta and involved in placental remodelling and embryo development.


Six out of fourteen genes had detectable expression in villi and for three genes the RNA and protein expression was altered due to maternal CNVs. These genes were integral to duplication on Xp22.2 (TRAPPC2 and OFD1) or disrupted by a duplication mapping to 17q25.3 (TIMP2). RNA and protein expression was increased for TRAPPC2 and OFD1 and reduced for TIMP2 in carrier miscarriages. The three genes have roles in processes important for pregnancy development such as extracellular matrix homeostasis (TIMP2 and TRAPPC2) and cilia function (OFD1). TIMP2 allelic expression was not affected by the CNV in miscarriages in comparison to control elective terminations.


We propose that functional studies of CNVs could help determine if and how the miscarriage CNVs affect the expression of integral genes. In case of parental CNVs, assessment of the function of their integral genes in parental reproductive tissues should be also considered in the future, especially if they affect processes relevant for pregnancy development and support.


Copy number variation; Gene expression; Miscarriage; OFD1; TIMP2; TRAPPC2

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