Mutation update for the NR5A1 gene involved in DSD and infertility

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Human mutation; v. 41, n. 1, p. 58-68, JAN 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 15/04763-4 - Application of whole exome sequencing to identify pathogenic variants in 46,XY partial gonadal dysgenesis
• Grantee: Andrea Trevas Maciel Guerra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/19445-6 - TRANSCRIPTOME AND WHOLE EXOME SEQUENCING TO ELUCIDATE DIFFERENT PHENOTYPES OF DISORDERS OF SEXUAL DEVELOPMENT IN 46,XY PATIENTS
• Grantee: Helena Fabbri Scallet
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/05603-5 - Functional analyses of new nucleotide variations in NR5A1 gene in patients 46,XY with disorders of sex development
• Grantee: Helena Fabbri Scallet
• Support Opportunities: Scholarships in Brazil - Doctorate