Mutation update for the NR5A1 gene involved in DSD and infertility
Mutation update for the NR5A1 gene involved in DSD and infertility
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DOI：
10.1002/humu.23916
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发表时间：
2019-09-27
期刊：
影响因子：
3.9
通讯作者：
de Mello, Maricilda Palandi
中科院分区：
文献类型：
--
作者：
Fabbri-Scallet, Helena;de Sousa, Lizandra Maia;de Mello, Maricilda Palandi
核受体亚家族5 A组成员1（NR 5A 1），也称为类固醇生成因子1，是一种必需的转录因子，调节许多对正常生殖生理和内分泌功能至关重要的靶基因。它由NR 5A 1基因编码，主要在类固醇生成组织中高剂量表达，在那里它控制肾上腺和性腺发育的几个步骤。NR 5A 1突变与广泛的性别发育障碍/差异表型谱（DSD）相关，DSD是一组染色体、性腺或解剖性别发育不典型的疾病。本文对238例NR 5A 1基因突变的临床资料进行回顾性分析。此外，我们报告的变化p.Ser4*，p。（Cys55Ser），p.（Met 78 Leu）和p.Met98Glyfs*45，它们之前没有被注释为NR 5A 1，并且在我们自己的队列的205个46，XY患者中的一些中被鉴定。这是第一个NR 5A 1突变的审查，其中包括46，XX和46，XY核型，目的是讨论的复杂性，基因型-表型之间的关系，在DSD和不育男性患者，也与原发性卵巢功能衰竭的女性。
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.