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.
Methods/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.
- Hydatidiform mole
- reproductive wastage
- spontaneous abortion
- molecular genetics
- immunology (including allergy)
- obstetrics and gynaecology
- reproductive medicine
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HM Collaborative Group Seang Lin Tan (Montréal, Canada), Alice Benjamin (Montréal, Canada), Lucy Gilbert (Montréal, Canada), Francois Golfier (Montpellier, France), Magali Breguet (Montréal, Canada), Radhika Srinivasan (Chandigarh, India), Adnan El-Hassan (Amman, Jordan), Feodora Stipoljev (Zagreb, Croatia), Srinivasan Krishnamurty (Montréal, Canada), Muhieddine Seoud (Beirut, Lebanon), Ghazi Zaatari (Beirut, Lebanon), Deborah Cohen (Montréal, Canada), Isabelle Girard (Montréal, Canada), R J McKinlay Gardner (Auckland, NewZealand).
Funding RS is supported by a Chercheur Boursier Salary Award, Senior from the FRSQ. CM was supported by a trainee award from the McGill Centre for the Study of Reproduction. RDRB was supported by a CREATE Scholarship from the ‘Reseau Quebecois en Reproduction’. This work is supported by the CIHR (grant number MOP 86546) and the French Ministry of Health to IT.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the McGill Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.