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

書誌事項

公開日
2015-09-01
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/ncomms9086
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>trans</jats:italic>-acting mutations have been found. Here we report mutations in <jats:italic>NLRP5</jats:italic> in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, <jats:italic>NLRP7</jats:italic> and <jats:italic>NLRP2</jats:italic>, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with <jats:italic>NLRP5</jats:italic> 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. <jats:italic>NLRP5</jats:italic> mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting.</jats:p>

収録刊行物

  • Nature Communications

    Nature Communications 6 (1), 8086-, 2015-09-01

    Springer Science and Business Media LLC

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