title: Novel NLRP7 mutations in familial recurrent hydatidiform mole: are NLRP7 mutations a risk for recurrent reproductive wastage?
abstract: OBJECTIVE
  Familial recurrent hydatidiform mole is an exceedingly rare clinical condition. Affected women are predisposed to molar pregnancies of diploid, biparental origin rather than androgenetic origin. At present, NLRP7 and KHDC3L (C6orf221) are the only genes known to be associated with familial recurrent hydatidiform mole. This study investigated the genetic dispositions in two large Turkish families with recurring molar conceptuses.
  
  
  METHODS
  Copy number variation analysis was performed followed by NLRP7 gene sequencing. The finding of a mono-allelic condition in one family led to investigation of the adjacent NLRP2 gene and recently associated KHDC3L gene. Sampled molar tissues were genotyped using microsatellite markers.
  
  
  RESULTS
  In one family, a homozygous single nucleotide insertion that caused a frameshift leading to an early stop codon, c.2940_2941insC (p.Glu981ArgfsX13), was identified in the affected sisters. In the other family, a heterozygous 60-kb deletion eliminating substantial portions of the NLRP2 and NLRP7 genes on one allele was found. Screening of NLRP2 and KHDC3L genes revealed no alterations that were considered to be pathological. Genotyping of six independent molar conceptions revealed that five were of diploid, biparental origin and one was of diandric, triploid origin.
  
  
  CONCLUSIONS
  Two novel protein-truncating mutations in the NLRP7 gene were found to be associated with familial recurrent hydatidiform mole. Mutations in the NLRP7 gene causing recurrent biparental hydatidiform mole may also be associated with other forms of recurrent reproductive wastage.
authors.affiliation: Department of Obstetrics and Gynaecology, Oncology Unit, Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey. Electronic address: drvolkanulker@yahoo.com.
authors.forename: V
authors.initials: V
authors.lastname: Ulker
authors.forename: H
authors.initials: H
authors.lastname: Gurkan
authors.forename: H
authors.initials: H
authors.lastname: Tozkir
authors.forename: V
authors.initials: V
authors.lastname: Karaman
authors.forename: H
authors.initials: H
authors.lastname: Ozgur
authors.forename: C
authors.initials: C
authors.lastname: Numanoglu
authors.forename: A
authors.initials: A
authors.lastname: Gedikbasi
authors.forename: O
authors.initials: O
authors.lastname: Akbayir
authors.forename: Z O
authors.initials: ZO
authors.lastname: Uyguner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D012008:Recurrence
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; C502448:NLRP7 protein, human
keywords: Familial recurrent hydatidiform mole; KHDC3L; NLRP7; Recurrent reproductive wastage