| [PMID]: | 27855412 |
| [Au] Autor: | Swartz JM; Ciarlo R; Guo MH; Abrha A; Weaver B; Diamond DA; Chan YM; Hirschhorn JN |
| [Ad] Endereço: | Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA. |
| [Ti] Título: | A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant. |
| [So] Source: | Horm Res Paediatr;87(3):191-195, 2017. |
| [Is] ISSN: | 1663-2826 |
| [Cp] País de publicação: | Switzerland |
| [La] Idioma: | eng |
| [Ab] Resumo: | BACKGROUND: A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD). This amino acid change impacts the DNA-binding domain and perturbs gonadal differentiation pathways. METHODS: Whole-exome sequencing was performed on a 46,XX subject with ovotesticular DSD. RESULTS: Exome results identified a heterozygous NR5A1 variant, p.Arg92Gln, in the 46,XX ovotesticular DSD proband. This arginine-to-glutamine change has been previously reported in the homozygous state in a 46,XY patient with gonadal and adrenal dysgenesis, though 46,XY and 46,XX heterozygous carriers of this variant have not been previously reported to have any clinical phenotype. CONCLUSIONS: The NR5A1 p.Arg92Gln variant, which has thus far only been seen in a family with 46,XY DSD, most likely contributes to the ovotesticular DSD in this case. In light of the recent reports of unrelated 46,XX subjects with testicular or ovotesticular DSD with the NR5A1 variant p.Arg92Trp, it appears that other mutations in the DNA binding domain have the potential to impact the factors determining testicular and ovarian differentiation. This case demonstrates the variability of phenotypes with the same genotype and broadens our understanding of the role of SF-1 in gonadal differentiation. |
| [Mh] Termos MeSH primário: |
Transtornos 46, XX do Desenvolvimento Sexual/genética
Mutação de Sentido Incorreto
Transtornos Ovotesticulares do Desenvolvimento Sexual/genética
Fator Esteroidogênico 1/genética
|
| [Mh] Termos MeSH secundário: |
Transtornos 46, XX do Desenvolvimento Sexual/patologia
Substituição de Aminoácidos
Pré-Escolar
Feminino
Seres Humanos
Transtornos Ovotesticulares do Desenvolvimento Sexual/patologia
Domínios Proteicos
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| [Pt] Tipo de publicação: | CASE REPORTS; JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (NR5A1 protein, human); 0 (Steroidogenic Factor 1) |
| [Em] Mês de entrada: | 1705 |
| [Cu] Atualização por classe: | 170522 |
[Lr] Data última revisão:
| 170522 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161118 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1159/000452888 |
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