Mutation update for the NR5A1 gene involved in DSD and infertility

Autor(es)

Fabbri-Scallet, Helena ^[1] ; de Sousa, Lizandra Maia ^[1] ; Maciel-Guerra, Andrea Trevas ^{[2, 3]} ; Guerra-Junior, Gil ^{[2, 4]} ; de Mello, Maricilda Palandi ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Ctr Mol Biol & Genet Engn CBMEG, BR-13083875 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Interdisciplinary Grp Study Sex Determinat & Diff, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet & Genom Med, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Fac Med Sci, Dept Pediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Human mutation; v. 41, n. 1, p. 58-68, JAN 2020.
• Citações Web of Science: 0

Resumo

Nuclear receptor subfamily 5 group A member 1 (NR5A1), also named steroidogenic factor 1, is an essential transcription factor that regulates a number of target genes crucial for normal reproductive physiology and endocrine function. It is encoded by NR5A1 gene and is expressed in high doses mainly in steroidogenic tissues, where it controls several steps of adrenal and gonadal development. NR5A1 mutations are associated with a wide phenotypic spectrum of disorders/differences of sex development (DSD), a group of conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. Here, we reviewed 188 NR5A1 mutations from 238 cases reported in literature so far. Additionally, we report the variations p.Ser4{*}, p.(Cys55Ser), p.(Met78Leu), and p.Met98Glyfs{*}45, which have not been annotated for NR5A1 before and were identified in some of the 205 46,XY patients of our own cohort. This is the first NR5A1 mutation review which includes both 46,XX and 46,XY karyotype, with the purpose of discussing the complexity of genotype-phenotype correlations among DSD and infertile male patients and also females with primary ovarian failure. (AU)

• Processo FAPESP: 15/04763-4 - Aplicação da técnica de sequenciamento do exoma para identificar mutações patogênicas na disgenesia gonadal parcial 46,XY
• Beneficiário: Andrea Trevas Maciel Guerra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/19445-6 - Uso das técnicas de transcriptoma, exoma e expressão gênica para elucidar diferentes fenótipos de distúrbios da diferenciação do sexo em pacientes 46,xy
• Beneficiário: Helena Fabbri Scallet
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/05603-5 - Estudo funcional de novas variações nucleotídicas no gene NR5A1 em pacientes 46,XY com distúrbios da diferenciação do sexo
• Beneficiário: Helena Fabbri Scallet
• Modalidade de apoio: Bolsas no Brasil - Doutorado