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Mutation update for the NR5A1 gene involved in DSD and infertility
Author(s) -
FabbriScallet Helena,
Sousa Lizandra Maia,
MacielGuerra Andréa Trevas,
GuerraJúnior Gil,
Mello Maricilda Palandi
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23916
Subject(s) - steroidogenic factor 1 , biology , infertility , gene , genetics , gonadal dysgenesis , phenotype , disorders of sex development , transcription factor , subfamily , nuclear receptor , endocrinology , pregnancy
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.