No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility
| Autor: | Lusine Aghajanova, Neil J. Sebire, Lesley Regan, Anneli Stavreus-Evers, I B Van den Veyver, Rosemary A. Fisher, Peter H. Dixon, Signe Altmäe, Sangeetha Mahadevan |
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| Rok vydání: | 2014 |
| Předmět: |
Infertility
Abortion Habitual medicine.medical_specialty DNA Mutational Analysis medicine.disease_cause Miscarriage Cohort Studies Pregnancy medicine Humans Adaptor Proteins Signal Transducing Unexplained infertility Gynecology Mutation business.industry Rehabilitation Female infertility Proteins Obstetrics and Gynecology Original Articles medicine.disease NLRP7 KH domain Reproductive Medicine Female Apoptosis Regulatory Proteins business Infertility Female |
| Zdroj: | Human Reproduction. 30:232-238 |
| ISSN: | 1460-2350 0268-1161 |
| DOI: | 10.1093/humrep/deu296 |
| Popis: | Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared. |
| Databáze: | OpenAIRE |
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