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

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

Author Santos, Mariza G. Google Scholar
Machado, Aline Z. Google Scholar
Martins, Conceicao N. Google Scholar
Domenice, Sorahia Google Scholar
Costa, Elaine M. F. Google Scholar
Nishi, Mirian Y. Google Scholar
Ferraz-de-Souza, Bruno Google Scholar
Jorge, Soraia A. C. Google Scholar
Pereira, Carlos A. Google Scholar
Soardi, Fernanda Caroline Google Scholar
Mello, Maricilda Palandi de Google Scholar
Maciel-Guerra, Andrea Trevas Google Scholar
Guerra Junior, Gil Google Scholar
Mendonca, Berenice B. Google Scholar
Institution Universidade de São Paulo (USP)
Inst Butantan
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Despite 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.
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number CNPq: 301339/20089
FAPESP: 05/04726-0
FAPESP: 07/512156
FAPESP: 10/51102-0
Date 2014-01-01
Published in Biomed Research International. New York: Hindawi Publishing Corporation, 8 p., 2014.
ISSN 2314-6133 (Sherpa/Romeo, impact factor)
Publisher Hindawi Publishing Corporation
Extent 8
Origin https://dx.doi.org/10.1155/2014/787465
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000338558100001
URI https://repositorio.unifesp.br/handle/11600/37154

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