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Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)
dc.contributor.authorModi, Bhavi P.
dc.contributor.authorTeves, Maria E.
dc.contributor.authorPearson, Laurel N.
dc.contributor.authorParikh, Hardik I.
dc.contributor.authorHaymond‐thornburg, Hannah
dc.contributor.authorTucker, John L.
dc.contributor.authorChaemsaithong, Piya
dc.contributor.authorGomez‐lopez, Nardhy
dc.contributor.authorYork, Timothy P.
dc.contributor.authorRomero, Roberto
dc.contributor.authorStrauss, Jerome F.
dc.date.accessioned2017-12-15T16:49:08Z
dc.date.available2019-01-07T18:34:38Zen
dc.date.issued2017-11
dc.identifier.citationModi, Bhavi P.; Teves, Maria E.; Pearson, Laurel N.; Parikh, Hardik I.; Haymond‐thornburg, Hannah ; Tucker, John L.; Chaemsaithong, Piya; Gomez‐lopez, Nardhy ; York, Timothy P.; Romero, Roberto; Strauss, Jerome F. (2017). "Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)." Molecular Genetics & Genomic Medicine 5(6): 720-729.
dc.identifier.issn2324-9269
dc.identifier.issn2324-9269
dc.identifier.urihttps://hdl.handle.net/2027.42/140041
dc.description.abstractBackgroundTwin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM.MethodsWe carried out whole exome sequencing (WES) of genomic DNA from neonates born of Africanâ American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls.ResultsWe identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases.ConclusionsWe conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in Africanâ Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.Rare damaging mutations in fetal innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by preterm premature rupture of membranes. An increased risk of preterm birth may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.
dc.publisherWiley Periodicals, Inc.
dc.publisherNational Academy Press
dc.subject.othermannoseâ binding lectin protein
dc.subject.otherAntimicrobial peptides
dc.subject.otherchorioamnionitis
dc.subject.otherdefensins
dc.subject.otherfucosyltransferase
dc.subject.otherinflammasome
dc.subject.otherinnate immunity
dc.subject.otherpreterm birth
dc.subject.otherpreterm premature rupture of membranes
dc.titleMutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelHuman Genetics
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/1/mgg3330.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/2/mgg3330_am.pdf
dc.identifier.doi10.1002/mgg3.330
dc.identifier.sourceMolecular Genetics & Genomic Medicine
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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