title: Recurrent pregnancy loss in a woman with NLRP7 mutation: not all molar pregnancies can be easily classified as either "partial" or "complete" hydatidiform moles.
abstract: Recurrent hydatidiform moles is an uncommon occurrence. Over the past decade, genetic studies of women with multiple recurrent molar pregnancies have revealed that maternal mutations in two different genes, NLRP7 and C6orf221, result in recurrent moles. We report a 23 year old woman, born of unrelated parents, who has experienced three molar pregnancies in succession. Whilst the first pregnancy was classified as a complete hydatidiform mole, the second and third moles defied classification as complete or partial mole using conventional histology, p57 nuclear staining pattern and ploidy studies. Molecular and cytogenetic studies proved that all three molar pregnancies were diploid and biparental in origin. Gene sequencing analysis showed that the patient is homozygous for a previously described mutation in NLRP7. A SNP microarray ruled out the presence of deletion of the NLRP7 locus. This case draws attention to the fact that recurrent molar pregnancies may be the result of specific, identifiable gene mutations, even in patients from non-consanguineous backgrounds. When pathologists encounter patients with molar pregnancies that are diploid and p57 negative and yet have fetal elements such as nucleated red blood cells or immature fetal tissues, it should heighten their suspicion of a possible genetic basis and appropriate molecular genetic workup performed with counseling offered.
authors.affiliation: Department of Obstetrics and Gynecology, University of Vermont, College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Brown
authors.forename: Sharon
authors.initials: S
authors.lastname: Mount
authors.forename: Ramesh
authors.initials: R
authors.lastname: Reddy
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
authors.forename: Cheung
authors.initials: C
authors.lastname: Wong
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.forename: Patrick
authors.initials: P
authors.lastname: Clifford
authors.forename: Laura
authors.initials: L
authors.lastname: Merrill
authors.forename: Stephen
authors.initials: S
authors.lastname: Brown
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D060005:Genotyping Techniques; D006801:Humans; D006828:Hydatidiform Mole / Q000145:classification / Q000235:genetics* / Q000473:pathology; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D011003:Ploidies; D011247:Pregnancy; D011248:Pregnancy Complications; D017422:Sequence Analysis, DNA; D014594:Uterine Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C502448:NLRP7 protein, human