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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...

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Autores principales: 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.
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
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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.
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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
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