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

2.50
Hdl Handle:
http://hdl.handle.net/11287/593987
Title:
Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans
Authors:
Docherty, L. E.; Rezwan, F. I.; Poole, R. L.; Turner, Claire L.; Kivuva, Emma; Maher, E. R.; Smithson, S. F.; Hamilton-Shield, J. P.; Patalan, M.; Gizewska, M.; Peregud-Pogorzelski, J.; Beygo, J.; Buiting, K.; Horsthemke, B.; Soellner, L.; Begemann, M.; Eggermann, T.; Baple, E.; Mansour, S.; Temple, I. K.; Mackay, D. J.
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.
Citation:
Nat Commun. 2015 Sep 1;6:8086.
Publisher:
Nature
Journal:
Nature communications
Issue Date:
1-Sep-2015
URI:
http://hdl.handle.net/11287/593987
DOI:
10.1038/ncomms9086
PubMed ID:
26323243
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26323243/
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
2041-1723
Appears in Collections:
2015 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorDocherty, L. E.en
dc.contributor.authorRezwan, F. I.en
dc.contributor.authorPoole, R. L.en
dc.contributor.authorTurner, Claire L.en
dc.contributor.authorKivuva, Emmaen
dc.contributor.authorMaher, E. R.en
dc.contributor.authorSmithson, S. F.en
dc.contributor.authorHamilton-Shield, J. P.en
dc.contributor.authorPatalan, M.en
dc.contributor.authorGizewska, M.en
dc.contributor.authorPeregud-Pogorzelski, J.en
dc.contributor.authorBeygo, J.en
dc.contributor.authorBuiting, K.en
dc.contributor.authorHorsthemke, B.en
dc.contributor.authorSoellner, L.en
dc.contributor.authorBegemann, M.en
dc.contributor.authorEggermann, T.en
dc.contributor.authorBaple, E.en
dc.contributor.authorMansour, S.en
dc.contributor.authorTemple, I. K.en
dc.contributor.authorMackay, D. J.en
dc.date.accessioned2016-01-19T12:38:18Zen
dc.date.available2016-01-19T12:38:18Zen
dc.date.issued2015-09-01en
dc.identifier.citationNat Commun. 2015 Sep 1;6:8086.en
dc.identifier.issn2041-1723en
dc.identifier.pmid26323243en
dc.identifier.doi10.1038/ncomms9086en
dc.identifier.urihttp://hdl.handle.net/11287/593987en
dc.description.abstractHuman-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.en
dc.language.isoengen
dc.publisherNatureen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26323243/en
dc.titleMutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humansen
dc.typeJournal Articleen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalNature communicationsen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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