title: NLRP7 in the spectrum of reproductive wastage: rare non-synonymous variants confer genetic susceptibility to recurrent reproductive wastage.
abstract: BACKGROUND
  NLRP7 mutations are responsible for recurrent molar pregnancies and associated reproductive wastage. To investigate the role of NLRP7 in sporadic moles and other forms of reproductive wastage, the authors sequenced this gene in a cohort of 135 patients with at least one hydatidiform mole or three spontaneous abortions; 115 of these were new patients.
  
  
  RESULTS
  All mutations were reviewed and their number, nature and locations correlated with the reproductive outcomes of the patients and histopathology of their products of conception. The presence of NLRP7 mutations was demonstrated in two patients with recurrent spontaneous abortions, and some rare non-synonymous variants (NSVs), present in the general population, were found to be associated with recurrent reproductive wastage. These rare NSVs were shown to be associated with lower secretion of interleukin 1β and tumour necrosis factor and therefore to have functional consequences similar to those seen in cells from patients with NLRP7 mutations. The authors also attempted to elucidate the cause of stillbirths observed in 13% of the patients with NLRP7 mutations by examining available placentas of the stillborn babies and live births from patients with mutations or rare NSVs. A number of severe to mild placental abnormalities were found, all of which are known risk factors for perinatal morbidity.
  
  
  CONCLUSIONS
  The authors recommend close follow-up of patients with NLRP7 mutations and rare NSVs to prevent the death of the rare or reduced number of babies that reach term.
authors.affiliation: Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, Quebec, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Messaed
authors.forename: Wafaa
authors.initials: W
authors.lastname: Chebaro
authors.forename: Raphael B
authors.initials: RB
authors.lastname: Di Roberto
authors.forename: Cecile
authors.initials: C
authors.lastname: Rittore
authors.forename: Annie
authors.initials: A
authors.lastname: Cheung
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Arseneau
authors.forename: Ariel
authors.initials: A
authors.lastname: Schneider
authors.forename: Moy Fong
authors.initials: MF
authors.lastname: Chen
authors.forename: Kurt
authors.initials: K
authors.lastname: Bernishke
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
authors.forename: Lori
authors.initials: L
authors.lastname: Hoffner
authors.forename: Philippe
authors.initials: P
authors.lastname: Sauthier
authors.forename: William
authors.initials: W
authors.lastname: Buckett
authors.forename: JianHua
authors.initials: J
authors.lastname: Qian
authors.forename: Nga Man
authors.initials: NM
authors.lastname: Lau
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bagga
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.forename: Philippe
authors.initials: P
authors.lastname: Coullin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000022:Abortion, Spontaneous / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D054238:Perinatal Mortality; D010920:Placenta / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053583:Interleukin-1beta; D050505:Mutant Proteins; C502448:NLRP7 protein, human; D014409:Tumor Necrosis Factor-alpha