Nr5a1 Loss-of-function Mutations Lead To 46,xy Partial Gonadal Dysgenesis Phenotype: Report Of Three Novel Mutations

dc.creatorFabbri
dc.creatorHelena C.; Ribeiro de Andrade
dc.creatorJuliana G.; Maciel-Guerra
dc.creatorAndrea T.; Guerra-Junior
dc.creatorGil; de Mello
dc.creatorMaricilda P.
dc.date2016
dc.date2017-11-13T13:23:21Z
dc.date2017-11-13T13:23:21Z
dc.date.accessioned2018-03-29T05:56:00Z
dc.date.available2018-03-29T05:56:00Z
dc.identifierSexual Development. Karger, v. 10, p. 191 - 199, 2016.
dc.identifier1661-5425
dc.identifier1661-5433
dc.identifierWOS:000386412900003
dc.identifier10.1159/000448013
dc.identifierhttps://www.karger.com/Article/Abstract/448013
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/328079
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1365104
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionMutations in the NR5A1 gene, which encodes the steroidogenic factor 1 (SF1), are responsible for different phenotypes of disorders of sex development (DSD), such as bilateral anorchia and hypospadias. Furthermore, they can be associated with primary amenorrhea, premature ovarian failure, male infertility, adrenal tumors, and endometriosis. Direct sequencing of the 7 NR5A1 exons including similar to 1,000 bp of the 5'-upstream and 3'-downstream regions and all intron-exon boundaries was performed in patients with DSD. Three different in silico tools were used to assess the consequences of a splice site mutation. As a result, 3 novel NR5A1 mutations were identified in 3 patients with 46,XY partial gonadal dysgenesis: p.Lys38* and p.Leu80Trpfs*8 lead to premature translation termination codons within the SF1 DNA-binding domain, and the intronic nucleotide substitution c.1138+1G>T at the intron 6 donor splice site is considered to modify correct splicing. We assume that the anomalous mRNA produced as a result of plys38* and p.Leu80Trpfs*8 will be degraded by nonsense-mediated mRNA decay even before translation, leading to SF1 haploinsufficiency. The c.1138+1G>T mutation is expected to produce a truncated protein. Heterozygous SF1 loss-of-function mutations in these cases resulted in mild DSD manifestations, such as dysgenetic testes, spontaneous puberty, and preserved adrenal function. (C) 2016 S. Karger AG, Basel.
dc.description10
dc.description4
dc.description191
dc.description199
dc.descriptionConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq - Brasil)
dc.descriptionFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/05603-5]
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageEnglish
dc.publisherKarger
dc.publisherBasel
dc.relationSexual Development
dc.rightsfechado
dc.sourceWOS
dc.subjectDisorders Of Sexual Development
dc.subjectHaploinsufficiency
dc.subjectNr5a1 Mutation
dc.subjectSf1 Protein
dc.titleNr5a1 Loss-of-function Mutations Lead To 46,xy Partial Gonadal Dysgenesis Phenotype: Report Of Three Novel Mutations
dc.typeArtículos de revistas


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