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The mutational spectrum of WT1 in male infertility

2014-11-11Journal article Restricted access
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dc.contributor.authorSeabra, Catarina M.
dc.contributor.authorQuental, Sofia
dc.contributor.authorLima, Ana C
dc.contributor.authorCarvalho, Filipa
dc.contributor.authorGonçalves, João
dc.contributor.authorFernandes, Susana
dc.contributor.authorPereira, Iris
dc.contributor.authorSilva, Júlia
dc.contributor.authorMarques, Patrícia I.
dc.contributor.authorSousa, Mário
dc.contributor.authorBarros, Alberto
dc.contributor.authorSeixas, Susana
dc.contributor.authorAmorim, António
dc.contributor.authorLopes, Alexandra M.
dc.date.accessioned2015-01-29T15:12:17Z
dc.date.available2015-01-29T15:12:17Z
dc.date.issued2014-11-11
dc.description.abstractPURPOSE: We evaluated the impact of WT1 mutations in isolated severe spermatogenic impairment in a population of European ancestry. WT1 was first identified as the gene responsible for Wilms tumor. It was later associated with a plethora of clinical phenotypes often accompanied by urogenital defects and male infertility. The recent finding of WT1 missense mutations in Chinese azoospermic males without major gonadal malformations broadened the phenotypic spectrum of WT1 defects and motivated this study. MATERIALS AND METHODS: We analyzed the WT1 coding region in a cohort of 194 Portuguese patients with nonobstructive azoospermia and in 188 with severe oligozoospermia with increased depth for the exons encoding the regulatory region of the protein. We also analyzed a group of 31 infertile males with a clinical history of unilateral or bilateral cryptorchidism and 1 patient with anorchia. RESULTS: We found 2 WT1 missense substitutions at higher frequency in patients than in controls. 1) A novel variant in exon 1 (p.Pro130Leu) that disrupted a mammalian specific polyproline stretch in the self-association domain was more frequent in azoospermia cases (0.27% vs 0.13%, p = 0.549). 2) A rare variant in a conserved residue in close proximity to the first zinc finger (pCys350Arg) was more frequent in severe oligozoospermia cases (0.80% vs 0.13%, p = 0.113). CONCLUSIONS: Results suggest a role for rare WT1 damaging variants in severe spermatogenic failure in populations of European ancestry. Large multicenter studies are needed to fully assess the contribution of WT1 genetic alterations to male infertility in the absence of other disease phenotypes.por
dc.identifier.citationJ Urol. 2015 May;193(5):1709-15. doi: 10.1016/j.juro.2014.11.004. Epub 2014 Nov 11.por
dc.identifier.doi10.1016/j.juro.2014.11.004
dc.identifier.issn0022-5347
dc.identifier.urihttp://hdl.handle.net/10400.18/2710
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevier/American Urological Association (AUA)por
dc.relationPTDC/SAU-NEU/101229/2008por
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0022534714048320por
dc.subjectWT1por
dc.subjectInfertilitypor
dc.subjectDoenças Genéticaspor
dc.subjectMale Infertilitypor
dc.subjectSpermatogenesispor
dc.subjectWilms Tumorpor
dc.subjectEuropean Continental Ancestry Grouppor
dc.subjectGenespor
dc.subjectMutationpor
dc.subjectTestispor
dc.titleThe mutational spectrum of WT1 in male infertilitypor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUSApor
oaire.citation.endPagepii: S0022-5347(14)04832-0por
oaire.citation.startPagepii: S0022-5347(14)04832-0por
oaire.citation.titleJournal of Urologypor
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

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