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A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles


NLRP7 is a maternal-effect gene that has a primary role in the oocyte. Its biallelic mutations are a major cause for recurrent diploid biparental hydatidiform moles (HMs). Here, we describe the full characterization of four HMs from a patient with a novel homozygous protein-truncating mutation in NLRP7. We found that some HMs have features of both complete and partial moles. Two HMs expressed p57 in the cytotrophoblast and stromal cells and exhibited divergent and discordant immunostaining. Microsatellite DNA-genotyping demonstrated that two HMs are diploid biparental and one is triploid digynic due to the failure of meiosis II. FISH analysis demonstrated triploidy in the cytotrophoblast and stromal cells in all villi. Our data highlight the atypical features of HM from patients with recessive NLRP7 mutations and the important relationship between NLRP7 defects in the oocyte and p57 expression that appear to be the main contributor to the molar phenotype regardless of the zygote genotype.

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We are grateful to Drs A. Buenerd, J.P. Machayekhi, and Y. Suignard for kindly providing the blocks from the four POCs for the study.

Author information

FA, RS: general supervision, drafting of the manuscript and preparation of the final text.

FA, LGD, NM, RS: performing of the molecular analysis, interpretation of data.

NM, RS: performing the sequencing.

FA, LGD, MDS, LH, US: pathological evaluation.

LH, US: performing of the FISH analysis, data interpretation.

TH: collection of the data.

PAB, FG, JM: involved in patient management and follow-up, provided clinical data.

All authors read and approved the final manuscript.

Correspondence to Fabienne Allias.

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The patient signed a written informed consent in accordance with the Declaration of Helsinki.

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Allias, F., Mechtouf, N., Gaillot-Durand, L. et al. A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles. Virchows Arch (2020). https://doi.org/10.1007/s00428-020-02769-w

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  • Recurrent hydatidiform mole
  • NLRP7
  • Mutation
  • p57
  • Digynic triploidy
  • Genotyping