Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humansReport as inadecuate


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


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Publication Date: 2015-09-01

Publisher: Nature Publishing Group

Volume: 6

Number: 8086

Language: English

Type: Article

Metadata: Show full item record

Citation: Docherty, L. E., Rezwan, F. I., Poole, R. L., Turner, C. L. S., Kivuva, E., Maher, E. R., Smithson, S. F., et al. (2015). Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. 6 (8086)

Description: This is the final version. It first appeared at http://www.nature.com/ncomms/2015/150901/ncomms9086/full/ncomms9086.html.

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.

Sponsorship: L.E.D. and F.I.R. were supported by the Medical Research Council (MR/J000329/1). J.B.,K.B., B.H., L.S. M.B. and T.E. were supported by Bundesministerium fu¨r Bildung undForschung (grant number 01GM1513A and 01GM1513C) and C.T. was supported by anIpsen Fellowship Grant. The cohort ‘Imprinting Disorders-Finding out Why’ wasaccrued through the support of the Newlife Foundation for Disabled Children andthrough support from the Wessex NIHR clinical research network and NIHR WellcomeSouthampton clinical research facility. Funding for DNA collection and methylationanalysis of normal control samples was provided in part by the National Institutes ofHealth R01 AI091905-01, R01 AI061471 and R01 HL082925. ERM thanks ActionMedical Research for support.

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This record's URL: http://dx.doi.org/10.1038/ncomms9086https://www.repository.cam.ac.uk/handle/1810/251052

Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Author: Docherty, Louise E.Rezwan, Faisal I.Poole, Rebecca L.Turner, Claire L. S.Kivuva, EmmaMaher, Eamonn R.Smithson, Sarah F.Hamilton-Sh

Source: https://www.repository.cam.ac.uk/handle/1810/251052



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