Homozygous Inactivating Mutation in NANOS3 in Two Sisters with Primary Ovarian Insufficiency

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dc.contributor.authorSantos, Mariza G.
dc.contributor.authorMachado, Aline Z.
dc.contributor.authorMartins, Conceicao N.
dc.contributor.authorDomenice, Sorahia
dc.contributor.authorCosta, Elaine M. F.
dc.contributor.authorNishi, Mirian Y.
dc.contributor.authorFerraz-de-Souza, Bruno
dc.contributor.authorJorge, Soraia A. C.
dc.contributor.authorPereira, Carlos A.
dc.contributor.authorSoardi, Fernanda Caroline
dc.contributor.authorMello, Maricilda Palandi de
dc.contributor.authorMaciel-Guerra, Andrea Trevas
dc.contributor.authorGuerra Junior, Gil
dc.contributor.authorMendonca, Berenice B.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInst Butantan
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:34:57Z
dc.date.available2016-01-24T14:34:57Z
dc.date.issued2014-01-01
dc.description.abstractDespite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. the RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lysmutation in NANOS3 was identified in two sisters with primary amenorrhea. the substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. in vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. the identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.en
dc.description.affiliationUniv São Paulo, Fac Med, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42,Hosp Clin, BR-05403900 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Lab Carboidratos & Radioimunoensaios LIM 18, Hosp Clin, BR-05403900 São Paulo, Brazil
dc.description.affiliationInst Butantan, Lab Imunol Viral, BR-05503900 São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Fac Ciencias Med, Ctr Biol Mol & Engn Genet, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Fac Ciencias Med, Dept Med Genet, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Fac Ciencias Med, Dept Pediat, BR-13083970 Campinas, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDCNPq: 301339/20089
dc.description.sponsorshipIDFAPESP: 05/04726-0
dc.description.sponsorshipIDFAPESP: 07/512156
dc.description.sponsorshipIDFAPESP: 10/51102-0
dc.format.extent8
dc.identifierhttps://dx.doi.org/10.1155/2014/787465
dc.identifier.citationBiomed Research International. New York: Hindawi Publishing Corporation, 8 p., 2014.
dc.identifier.doi10.1155/2014/787465
dc.identifier.fileWOS000338558100001.pdf
dc.identifier.issn2314-6133
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/37154
dc.identifier.wosWOS:000338558100001
dc.language.isoeng
dc.publisherHindawi Publishing Corporation
dc.relation.ispartofBiomed Research International
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleHomozygous Inactivating Mutation in NANOS3 in Two Sisters with Primary Ovarian Insufficiencyen
dc.typeinfo:eu-repo/semantics/article
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