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

Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans
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 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.
Docherty, Louise E.
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Rezwan, Faisal I.
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Poole, Rebecca L.
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Turner, Claire L.S.
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Kivuva, Emma
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Maher, Eamonn R.
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Smithson, Sarah F.
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Hamilton-Shield, Julian P.
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Patalan, Michal
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Gizewska, Maria
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Peregud-Pogorzelski, Jaroslaw
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Beygo, Jasmin
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Buiting, Karin
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Horsthemke, Bernhard
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Soellner, Lukas
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Begemann, Matthias
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Eggermann, Thomas
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Baple, Emma
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Mansour, Sahar
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Temple, I. Karen
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Mackay, Deborah J.G.
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Docherty, Louise E.
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Rezwan, Faisal I.
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Poole, Rebecca L.
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Turner, Claire L.S.
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Kivuva, Emma
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Maher, Eamonn R.
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Smithson, Sarah F.
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Hamilton-Shield, Julian P.
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Patalan, Michal
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Gizewska, Maria
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Peregud-Pogorzelski, Jaroslaw
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Beygo, Jasmin
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Buiting, Karin
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Horsthemke, Bernhard
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Soellner, Lukas
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Begemann, Matthias
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Eggermann, Thomas
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Baple, Emma
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Mansour, Sahar
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Temple, I. Karen
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Mackay, Deborah J.G.
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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 and Mackay, Deborah J.G. (2015) Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Nature Communications, 6, [8086]. (doi:10.1038/ncomms9086). (PMID:26323243)

Record type: Article

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.

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Accepted/In Press date: 16 July 2015
e-pub ahead of print date: 1 September 2015
Published date: 1 September 2015
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 381349
URI: http://eprints.soton.ac.uk/id/eprint/381349
PURE UUID: 17452402-39fa-4128-8d10-d68dc8326385
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for I. Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781
ORCID for Deborah J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 24 Sep 2015 09:04
Last modified: 15 Mar 2024 03:45

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Contributors

Author: Louise E. Docherty
Author: Faisal I. Rezwan ORCID iD
Author: Rebecca L. Poole
Author: Claire L.S. Turner
Author: Emma Kivuva
Author: Eamonn R. Maher
Author: Sarah F. Smithson
Author: Julian P. Hamilton-Shield
Author: Michal Patalan
Author: Maria Gizewska
Author: Jaroslaw Peregud-Pogorzelski
Author: Jasmin Beygo
Author: Karin Buiting
Author: Bernhard Horsthemke
Author: Lukas Soellner
Author: Matthias Begemann
Author: Thomas Eggermann
Author: Emma Baple
Author: Sahar Mansour
Author: I. Karen Temple ORCID iD

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