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| [PMID]: | 28033660 |
| [Au] Autor: | Domenice S; Machado AZ; Ferreira FM; Ferraz-de-Souza B; Lerario AM; Lin L; Nishi MY; Gomes NL; da Silva TE; Silva RB; Correa RV; Montenegro LR; Narciso A; Costa EM; Achermann JC; Mendonca BB |
| [Ad] Endereço: | Sorahia Domenice, Aline Zamboni Machado, Bruno Ferraz-de-Souza, Antonio Marcondes Lerario, Mirian Yumie Nishi, Nathalia Lisboa Gomes, Thatiana Evelin da Silva, Rosana Barbosa Silva, Luciana R. Montenegro, Amanda Narciso, Elaine Maria Frade Costa, and Berenice Bilharinho Mendonca are from the Laborat |
| [Ti] Título: | Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals. |
| [So] Source: | Birth Defects Res C Embryo Today;108(4):309-320, 2016 12. | | [Is] ISSN: | 1542-9768 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309-320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc. |
| [Mh] Termos MeSH primário: |
Fator Esteroidogênico 1/genética
Fator Esteroidogênico 1/fisiologia
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| [Mh] Termos MeSH secundário: |
Adolescente
Insuficiência Adrenal
Adulto
Brasil
Criança
Pré-Escolar
Transtornos do Desenvolvimento Sexual/genética
Transtornos do Desenvolvimento Sexual/metabolismo
Feminino
Transtornos Gonadais/genética
Transtornos Gonadais/metabolismo
Seres Humanos
Lactente
Masculino
Mutação
Fenótipo
Insuficiência Ovariana Primária/genética
Insuficiência Ovariana Primária/metabolismo
Fator Esteroidogênico 1/metabolismo
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; REVIEW |
[Nm] Nome de substância:
| 0 (NR5A1 protein, human); 0 (Steroidogenic Factor 1) |
| [Em] Mês de entrada: | 1708 |
| [Cu] Atualização por classe: | 170823 |
[Lr] Data última revisão:
| 170823 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161230 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1002/bdrc.21145 |
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