Cargando…
Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568303/ https://www.ncbi.nlm.nih.gov/pubmed/26323243 http://dx.doi.org/10.1038/ncomms9086 |
_version_ | 1782389886819500032 |
---|---|
author | Docherty, Louise E. Rezwan, Faisal I. Poole, Rebecca L. Turner, Claire L. S. Kivuva, Emma Maher, Eamonn R. Smithson, Sarah F. Hamilton-Shield, Julian P. Patalan, Michal Gizewska, Maria Peregud-Pogorzelski, Jaroslaw Beygo, Jasmin Buiting, Karin Horsthemke, Bernhard Soellner, Lukas Begemann, Matthias Eggermann, Thomas Baple, Emma Mansour, Sahar Temple, I. Karen Mackay, Deborah J. G. |
author_facet | Docherty, Louise E. Rezwan, Faisal I. Poole, Rebecca L. Turner, Claire L. S. Kivuva, Emma Maher, Eamonn R. Smithson, Sarah F. Hamilton-Shield, Julian P. Patalan, Michal Gizewska, Maria Peregud-Pogorzelski, Jaroslaw Beygo, Jasmin Buiting, Karin Horsthemke, Bernhard Soellner, Lukas Begemann, Matthias Eggermann, Thomas Baple, Emma Mansour, Sahar Temple, I. Karen Mackay, Deborah J. G. |
author_sort | Docherty, Louise E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4568303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45683032015-09-14 Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans Docherty, Louise E. Rezwan, Faisal I. Poole, Rebecca L. Turner, Claire L. S. Kivuva, Emma Maher, Eamonn R. Smithson, Sarah F. Hamilton-Shield, Julian P. Patalan, Michal Gizewska, Maria Peregud-Pogorzelski, Jaroslaw Beygo, Jasmin Buiting, Karin Horsthemke, Bernhard Soellner, Lukas Begemann, Matthias Eggermann, Thomas Baple, Emma Mansour, Sahar Temple, I. Karen Mackay, Deborah J. G. Nat Commun Article 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. Nature Pub. Group 2015-09-01 /pmc/articles/PMC4568303/ /pubmed/26323243 http://dx.doi.org/10.1038/ncomms9086 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Docherty, Louise E. Rezwan, Faisal I. Poole, Rebecca L. Turner, Claire L. S. Kivuva, Emma Maher, Eamonn R. Smithson, Sarah F. Hamilton-Shield, Julian P. Patalan, Michal Gizewska, Maria Peregud-Pogorzelski, Jaroslaw Beygo, Jasmin Buiting, Karin Horsthemke, Bernhard Soellner, Lukas Begemann, Matthias Eggermann, Thomas Baple, Emma Mansour, Sahar Temple, I. Karen Mackay, Deborah J. G. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title | Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title_full | Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title_fullStr | Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title_full_unstemmed | Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title_short | Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
title_sort | mutations in nlrp5 are associated with reproductive wastage and multilocus imprinting disorders in humans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568303/ https://www.ncbi.nlm.nih.gov/pubmed/26323243 http://dx.doi.org/10.1038/ncomms9086 |
work_keys_str_mv | AT dochertylouisee mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT rezwanfaisali mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT poolerebeccal mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT turnerclairels mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT kivuvaemma mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT mahereamonnr mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT smithsonsarahf mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT hamiltonshieldjulianp mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT patalanmichal mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT gizewskamaria mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT peregudpogorzelskijaroslaw mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT beygojasmin mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT buitingkarin mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT horsthemkebernhard mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT soellnerlukas mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT begemannmatthias mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT eggermannthomas mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT bapleemma mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT mansoursahar mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT templeikaren mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans AT mackaydeborahjg mutationsinnlrp5areassociatedwithreproductivewastageandmultilocusimprintingdisordersinhumans |