ArticleThe Journal of clinical endocrinology and metabolism2007
Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function.
Article in The Journal of clinical endocrinology and metabolism, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 209 citations in OpenAlex.
- Refining the diagnosis of 46,XY disorders of sex development: insight from whole-exome sequencing.Orphanet journal of rare diseases · 2026Article
- Spectrum and genotype-phenotype correlation of NR5A1 variants in 46,XY DSD: a systematic review and meta-analysis.Endocrine connections · 2026Article
- Article
- Novel and recurrent genetic variants associated with male and female infertility.Journal of applied genetics · 2025Article
- Clinical Spectrum, Surgical Management, and Outcomes ofMedicina (Kaunas, Lithuania) · 2025Review
- Swyer Syndrome: A diagnostic challenge.JBRA assisted reproduction · 2025Article
- Characterization of 35 Novel NR5A1/SF-1 Variants Identified in Individuals With Atypical Sexual Development: The SF1next Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Population-Based Study of Rare Coding Variants inJournal of the Endocrine Society · 2024Article
- Role ofCurrent issues in molecular biology · 2024Review
- Case report: Rare heterozygous variant in theFrontiers in medicine · 2024Article
- Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development.EBioMedicine · 2024Article
- Steroidogenic Factor 1, a Goldilocks Transcription Factor from Adrenocortical Organogenesis to Malignancy.International journal of molecular sciences · 2023Review
- Case Report: Longitudinal follow-up and testicular sperm extraction in a patient with a pathogenicFrontiers in endocrinology · 2023Article
- Lrh1 can help reprogram sexual cell fate and is required for Sertoli cell development and spermatogenesis in the mouse testis.PLoS genetics · 2022Article
- Case Report: Severe Gonadal Dysgenesis Causing 46,XY Disorder of Sex Development Due to a NovelFrontiers in genetics · 2022Article
- Next Generation Sequencing Should Be Proposed to Every Woman With "Idiopathic" Primary Ovarian Insufficiency.Journal of the Endocrine Society · 2021Article
- Performance of mutation pathogenicity prediction tools on missense variants associated with 46,XY differences of sex development.Clinics (Sao Paulo, Brazil) · 2021Article
- Male pseudohermaphroditism: A case study of 46,XY disorder of sexual development using whole-exome sequencing.Clinical case reports · 2020Article
- Functional study of a novel c.630delG (p.Y211Tfs*85) mutation in NR5A1 gene in a Chinese boy with 46,XY disorders of sex development.Journal of assisted reproduction and genetics · 2020Article
- Primary adrenal insufficiency: New genetic causes and their long-term consequences.Clinical endocrinology · 2020Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
contextSteroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor transcription factor that plays a key role in regulating adrenal and gonadal development, steroidogenesis, and reproduction. Targeted deletion of Nr5a1 (Sf1) in the mouse results in adrenal and gonadal agenesis, XY sex-reversal, and persistent Müllerian structures in males. Consistent with the murine phenotype, human mutations in SF1 were described initially in two 46,XY individuals with female external genitalia, Müllerian structures (uterus), and primary adrenal failure.
objectiveGiven recent case reports of haploinsufficiency of SF1 affecting testicular function in humans, we aimed to identify SF1 mutations in a cohort of individuals with a phenotypic spectrum of 46,XY gonadal dysgenesis/impaired androgenization (now termed 46,XY disorders of sex development) with normal adrenal function. METHODS AND PATIENTS: The study included mutational analysis of NR5A1 in 30 individuals with 46,XY disorders of sex development, followed by functional studies of SF1 activity.
resultsHeterozygous missense mutations in NR5A1 were found in four individuals (four of 30, 13%) with this phenotype. These mutations (V15M, M78I, G91S, L437Q) were shown to impair transcriptional activation through abnormal DNA binding (V15M, M78I, G91S), altered subnuclear localization (V15M, M78I), or disruption of the putative ligand-binding pocket (L437Q). Two mutations appeared to be de novo or germline changes. The other two mutations appeared to be inherited in a sex-limited dominant manner because the mother is heterozygous for the change.
conclusionsThese studies demonstrate that SF1 mutations are more frequent than previously suspected causes of impaired fetal and postnatal testicular function in 46,XY individuals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.