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Mutations in NLRP7 are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles
  1. Peter H Dixon1,
  2. Pirada Trongwongsa1,
  3. Shadi Abu-Hayyah1,
  4. Sze Hwei Ng1,
  5. Syed Ali Akbar2,
  6. Nuzhat P Khawaja3,
  7. Michael J Seckl4,
  8. Philip M Savage4,
  9. Rosemary A Fisher1,4
  1. 1Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, UK
  2. 2Department of Genito-Urinary Medicine, Falkirk Community Hospital, Falkirk, UK
  3. 3Department of Obstetrics and Gynaecology, Sheikh Zayed Medical College, Rehim Yar Khan, Pakistan
  4. 4Department of Oncology, Imperial College Healthcare NHS, London, UK
  1. Correspondence to Dr Rosemary 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 been identified as the major gene involved in the inherited predisposition to recurrent molar pregnancies, a rare recessive condition in which affected individuals have complete hydatidiform moles of diploid biparental origin (BiCHM). The role of NLRP7 in other types of molar pregnancy and reproductive wastage has not been conclusively demonstrated. The purpose of this study was to clarify this by identifying NLRP7 variation in two clinically well-defined groups of patients: women with recurrent BiCHM, and women with three or more recurrent complete hydatidiform moles of proven androgenetic origin (AnCHM).

Methods Fluorescent microsatellite genotyping of molar tissue was used to establish a diagnosis of recurrent BiCHM (four novel cases) or recurrent AnCHM (nine women with multiple CHM). These two groups were subsequently screened for mutations in NLRP7 using DNA sequencing. Additional screening for non-pathological variants was performed in 21 previously published cases of recurrent BiCHM. Taqman genotyping was used to determine the frequency of novel NLRP7 variants in two control cohorts of Caucasian and Asian women with no adverse reproductive outcomes.

Results Of the four novel cases with recurrent BiCHM, two were homozygous for mutations in NLRP7 while one was a compound heterozygote for a nonsense mutation and a pathological variant. No NLRP7 mutations or pathological variants were identified in the fourth case. None of the women with AnCHM carried any mutations or pathological variants of NLRP7. A single case of AnCHM was found to be heterozygous for a novel variant (R413Q).

Conclusion NLRP7 mutations do not represent a major cause of AnCHM.

  • Diploid biparental hydatidiform mole
  • androgenetic hydatidiform mole
  • complete hydatidiform mole
  • NLRP7
  • single nucleotide polymorphism
  • developmental
  • metabolic disorders
  • molecular genetics
  • liver disease
  • obstetrics and gynaecology
  • genetics
  • clinical genetics
  • genetic screening/counselling
  • imprinting
  • oncology

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  • Funding PT was supported by a grant from the Cancer Treatment and Research Trust.

  • Competing interests None.

  • Patient consent This study involves several cohorts of patients for whom it would be impracticable to obtain consent retrospectively. All cases are fully anonymised, very little clinical information is provided for each individual, and no individual in the study can be identified.

  • Ethics approval Ethics approval was provided by Riverside Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional unpublished data from the study is available. Details of the assays used for SNP genotyping are available to readers on request.