NLRP genes and their role in preeclampsia and multi-locus imprinting disorders
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Lukas Soellner
und
Klaus Zerres
Abstract
Preeclampsia (PE) affects 2–5% of all pregnancies. It is a multifactorial disease, but it has been estimated that 35% of the variance in liability of PE are attributable to maternal genetic effects and 20% to fetal genetic effects. PE has also been reported in women delivering children with Beckwith-Wiedemann syndrome (BWS, OMIM 130650), a disorder associated with aberrant methylation at genomically imprinted loci. Among others, members of the NLRP gene family are involved in the etiology of imprinting defects. Thus, a functional link between PE, NLRP gene mutations and aberrant imprinting can be assumed. Therefore we analyzed a cohort of 47 PE patients for NLRP gene mutations by next generation sequencing. In 25 fetuses where DNA was available we determined the methylation status at the imprinted locus. With the exception of one woman heterozygous for a missense variant in the NLRP7 gene (NM_001127255.1(NLRP7):c.542G>C) we could not identify further carriers, in the fetal DNA normal methylation patterns were observed. Thus, our negative screening results in a well-defined cohort indicate that NLRP mutations are not a relevant cause of PE, though strong evidence for a functional link between NLRP mutations, PE and aberrant methylation exist.
Author’s statement
Conflict of interest: Authors state no conflict of interest.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
Funding: The authors LS and TE are supported by the Bundesministerium für Bildung und Forschung (Network “Imprinting Diseases”, 01GM1513B). TE, LS and MB are members of the COST Action BM1208 and EUCID.net (European congenital imprinting disorders network; www.imprinting-disorders.eu).
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Supplemental Material:
The online version of this article (DOI: https://doi.org/10.1515/jpm-2016-0405) offers supplementary material, available to authorized users.
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review article
- Fetal cardiac tumors: clinical features, management and prognosis
- Original articles – Obstetrics
- Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection
- Gaps in obstetric care processes – we can only improve what is being measured
- Tokophobia (fear of childbirth): prevalence and risk factors
- Adjuvant administration of 17-α-hydroxy-progesterone caproate in women with three or more second trimester pregnancy losses undergoing cervical cerclage is no more effective than cerclage alone
- The role of ultrasound in the prediction of birth weight discordance in twin pregnancies: are we there yet?
- NLRP genes and their role in preeclampsia and multi-locus imprinting disorders
- Original articles – Fetus
- Diagnostic value of perinatal autopsies: analysis of 486 cases
- Feto-maternal osmotic balance at term. A prospective observational study
- Original articles – Newborn
- Oxygen saturation trends in normal healthy term newborns: normal vaginal delivery vs. elective cesarean section
- Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark
- Critical congenital heart disease screening with a pulse oximetry in neonates
- DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma
- A non-invasive method to rule out transient tachypnea of the newborn (TTN): fetal pulmonary artery acceleration to ejection time ratio
- Letter to the Editor
- Clarification of the methods and statistics in the study “Planned home birth and the association with neonatal hypoxic ischemic encephalopathy”
- Clarification of the methods and statistics in the study “Planned home birth and the association with neonatal hypoxic ischemic encephalopathy”
- Reply to: Planned home birth and the association with neonatal hypoxic ischemic encephalopathy
- Response to the Letter to the Editor, “Risk factors of uterine rupture with a special interest to uterine fundal pressure: methodological issues”
- Re: Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review
Artikel in diesem Heft
- Frontmatter
- Review article
- Fetal cardiac tumors: clinical features, management and prognosis
- Original articles – Obstetrics
- Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection
- Gaps in obstetric care processes – we can only improve what is being measured
- Tokophobia (fear of childbirth): prevalence and risk factors
- Adjuvant administration of 17-α-hydroxy-progesterone caproate in women with three or more second trimester pregnancy losses undergoing cervical cerclage is no more effective than cerclage alone
- The role of ultrasound in the prediction of birth weight discordance in twin pregnancies: are we there yet?
- NLRP genes and their role in preeclampsia and multi-locus imprinting disorders
- Original articles – Fetus
- Diagnostic value of perinatal autopsies: analysis of 486 cases
- Feto-maternal osmotic balance at term. A prospective observational study
- Original articles – Newborn
- Oxygen saturation trends in normal healthy term newborns: normal vaginal delivery vs. elective cesarean section
- Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark
- Critical congenital heart disease screening with a pulse oximetry in neonates
- DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma
- A non-invasive method to rule out transient tachypnea of the newborn (TTN): fetal pulmonary artery acceleration to ejection time ratio
- Letter to the Editor
- Clarification of the methods and statistics in the study “Planned home birth and the association with neonatal hypoxic ischemic encephalopathy”
- Clarification of the methods and statistics in the study “Planned home birth and the association with neonatal hypoxic ischemic encephalopathy”
- Reply to: Planned home birth and the association with neonatal hypoxic ischemic encephalopathy
- Response to the Letter to the Editor, “Risk factors of uterine rupture with a special interest to uterine fundal pressure: methodological issues”
- Re: Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review
