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Research Article

Mutations in NLRP7 and KHDC3L Confer a Complete Hydatidiform Mole Phenotype on Digynic Triploid Conceptions

  1. Masoumeh Fallahian1,
  2. Neil J. Sebire2,
  3. Philip M. Savage2,
  4. Michael J. Seckl2,
  5. Rosemary A. Fisher2,3,*

Article first published online: 2 NOV 2012

DOI: 10.1002/humu.22228

Issue

Human Mutation

Human Mutation

Volume 34, Issue 2, pages 301–308, February 2013

Additional Information

How to Cite

Fallahian, M., Sebire, N. J., Savage, P. M., Seckl, M. J. and Fisher, R. A. (2013), Mutations in NLRP7 and KHDC3L Confer a Complete Hydatidiform Mole Phenotype on Digynic Triploid Conceptions. Hum. Mutat., 34: 301–308. doi: 10.1002/humu.22228

Author Information

  1. 1

    Department of Obstetrics and Gynecology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

  2. 2

    Trophboblastic Tumour Screening and Treatment Centre, Department of Oncology, Imperial College London, Charing Cross Campus, London, United Kingdom

  3. 3

    Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom

* Correspondence to: Rosemary A Fisher, FRCPath, Room 3009, Institute of Reproductive and Developmental Biology, Hammersmith Campus, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom. E-mail: r.fisher@imperial.ac.uk

  1. Contract grant sponsors: Hammersmith Hospitals Trustees’ Research Committee (60312); Cancer Treatment and Research Trust (p11407).

  2. Communicated by Graham R. Taylor

Publication History

  1. Issue published online: 29 JAN 2013
  2. Article first published online: 2 NOV 2012
  3. Accepted manuscript online: 11 OCT 2012 01:10PM EST
  4. Manuscript Accepted: 13 SEP 2012
  5. Manuscript Received: 11 MAY 2012

Funded by

  • Hammersmith Hospitals Trustees’ Research Committee. Grant Number: 60312
  • Cancer Treatment and Research Trust. Grant Number: p11407

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Keywords:

  • hydatidiform mole;
  • NLRP7;
  • KHDC3L;
  • C6orf221;
  • digynic triploidy

ABSTRACT

Digynic triploidy is classically associated with a severely growth restricted fetus and a small nonmolar placenta. However, in genotyping hydatidiform moles as part of clinical practice, we identified two digynic triploid conceptions presenting with histopathological features of classical complete hydatidiform mole (CHM). Both cases occurred in women with a history of previous molar pregnancies and no normal pregnancies. Pathological review and genotyping of other molar pregnancies in these cases showed them to be typical CHM with negative p57KIP2 immunostaining of the cytotrophoblast cells and villous stroma and to be diploid but biparental, confirming a diagnosis of familial recurrent hydatidiform mole (FRHM). Mutation screening of NLRP7 had identified a homozygous duplication, leading to a truncated protein, in case 1 whereas mutation screening of KHDC3L (C6orf221) in case 2 showed both the proband and her sister to be compound heterozygotes for mutations in KHDC3L. The observation of a single digynic, triploid conception presenting as a CHM in women with FRHM, where other pregnancies are diploid and biparental, supports the hypothesis that the role of both NLRP7 and KHDC3L in pregnancy is in setting and/or maintaining the maternal imprint. Clinically, a diagnosis of FRHM should be considered in women with genetically unusual conceptions that are phenotypically CHM.

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