Format

Send to

Choose Destination
Nat Commun. 2015 Sep 1;6:8086. doi: 10.1038/ncomms9086.

Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans.

Author information

1
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
2
Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury SP2 8BJ, UK.
3
Peninsula Clinical Genetics Service, Royal Devon and Exeter Hospital, Exeter EX1 2ED, UK.
4
Department of Medical Genetics, University of Cambridge, and Cambridge NIHR Biomedical Research Centre, Addenbrooke's Hospital, Cambridge CP2 0QQ, UK.
5
Department of Clinical Genetics, University Hospitals Bristol, Bristol BS2 8EG, UK.
6
School of Clinical Sciences, University of Bristol, Bristol BS2 8AE, UK.
7
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 71-252, Szczecin, Poland.
8
Department of Paediatric Oncology, Pomeranian Medical University, 71-252 Szczecin, Poland.
9
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstr 55, 45122 Essen, Germany.
10
Institut für Humangenetik, University Hospital, RWTH Aachen, Pauwelsstr 30, 52074 Aachen, Germany.
11
Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton SO16 5YA, UK.
12
St George's Healthcare NHS Trust, University of London, London, SW17 0QT UK.

Abstract

Human-imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of parent of origin-specific DNA methylation at imprinted loci across the genome. Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found. Here we report mutations in NLRP5 in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with NLRP5 mutations have heterogenous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage. NLRP5 mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting.

PMID:
26323243
PMCID:
PMC4568303
DOI:
10.1038/ncomms9086
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center