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Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region
  1. C M Wang1,
  2. P H Dixon1,
  3. S Decordova1,
  4. M D Hodges2,
  5. N J Sebire2,
  6. S Ozalp3,
  7. M Fallahian4,
  8. A Sensi5,
  9. F Ashrafi6,
  10. V Repiska7,
  11. J Zhao8,
  12. Y Xiang8,
  13. P M Savage2,
  14. M J Seckl2,
  15. R A Fisher1,2
  1. 1
    Institute of Reproductive and Developmental Biology, Imperial College London, UK
  2. 2
    Trophboblastic Tumour Screening and Treatment Centre, Department of Oncology, Imperial College London, UK
  3. 3
    Department of Obstetrics and Gynaecology, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey
  4. 4
    Department of Obstetrics and Gynaecology, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
  5. 5
    Università di Ferrara, Genetica Medica, Ferrara, Italy
  6. 6
    Department of Obstetrics and Gynaecology, Rockhampton Base Hospital, Queensland, Australia
  7. 7
    Institute of Medical Biology, Comenius University, Bratislava, Slovakia
  8. 8
    Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Beijing, China
  1. Dr R A Fisher, Gestational Trophoblastic Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK; r.fisher{at}


Background: NLRP7 (NALP7) has recently been identified as the causative gene for familial recurrent hydatidiform mole (FRHM), a rare autosomal recessive condition in which affected women have recurrent molar pregnancies of diploid biparental origin. To date only a small number of affected families have been described. Our objectives were to investigate the diversity of mutations and their localisation to one or both isoforms of NLRP7, by screening a large series of women with FRHM and to examine the normal expression of NLRP7 in ovarian tissue.

Methods: Fluorescent microsatellite genotyping of molar tissue was used to establish a diagnosis of FRHM. Twenty families were subsequently screened for mutations in NLRP7 using DNA sequencing. Expression of NLRP7 in the ovary was examined by immunohistochemical staining.

Results: 16 different mutations were identified in the study, 13 of which were novel. Missense mutations were found to be present in transcript variant 2 of NLRP7 and cluster in the leucine-rich region (LRR). A man with two affected sisters and homozygous for the p.R693P mutation had normal reproductive outcomes. In the normal human ovary, NLRP7 expression is confined to the oocytes and present at all stages from primordial to tertiary follicles.

Conclusion: 13 novel mutations in NLRP7 were identified. We confirm that mutations in NLRP7 affect female but not male reproduction, and provide evidence that transcript variant 2 of NLRP7 is the important isoform in this condition. The mutation clustering seen confirms that the LRR is critical for normal functioning of NLRP7.

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  • ▸ A supplementary table is published online only at

  • Funding: This work was supported by grants from the Hammersmith Hospitals Trust Research Committee, Cancer Treatment and Research Trust and the Wellcome Trust.

  • Competing interests: None.