ArticleThe Journal of clinical endocrinology and metabolism2010
Concomitant mutations in the P450 oxidoreductase and androgen receptor genes presenting with 46,XY disordered sex development and androgenization at adrenarche.
Article in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature.Journal of endocrinological investigation · 2023Pooled it
- Persistent progesterone elevation in infertility revealing non-classic P450 oxidoreductase deficiency: 2 cases.JCEM case reports · 2026Article
- 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
- Exploring Novel Variants of the Cytochrome P450 Reductase Gene (Biomolecules · 2023Article
- In Silico Analysis of PORD Mutations on the 3D Structure of P450 Oxidoreductase.Molecules (Basel, Switzerland) · 2022Article
- Normal and Premature Adrenarche.Endocrine reviews · 2021Review
- Oligogenic Origin of Differences of Sex Development in Humans.International journal of molecular sciences · 2020Review
- Monogenic Disorders of Adrenal Steroidogenesis.Hormone research in paediatrics · 2018Review
- Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity.The Journal of clinical endocrinology and metabolism · 2016Article
- Pharmacogenomics of human P450 oxidoreductase.Frontiers in pharmacology · 2014Review
- Prenatal diagnosis of congenital adrenal hyperplasia caused by P450 oxidoreductase deficiency.The Journal of clinical endocrinology and metabolism · 2013Article
- Evidence for DNA-binding domain--ligand-binding domain communications in the androgen receptor.Molecular and cellular biology · 2012Article
- Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.The Journal of clinical endocrinology and metabolism · 2012Article
- Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.The Journal of clinical endocrinology and metabolism · 2011Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
contextUndervirilization in males, i.e. 46,XY disordered sex development (46,XY DSD), is commonly caused by either lack of androgen action due to mutant androgen receptor (AR) or deficient androgen synthesis, e.g. due to mutations in 17alpha-hydroxylase (CYP17A1). Like all other microsomal cytochrome P450 (CYP) enzymes, CYP17A1 requires electron transfer from P450 oxidoreductase (POR).
objectiveThe objective of the study was to analyze the clinical and biochemical phenotype in a 46,XY individual carrying concomitant POR and AR mutations and to dissect their impact on phenotypic expression.
methodsWe characterized the clinical and biochemical phenotype, genetic identification, and functional analysis of POR missense mutation by yeast micrososomal coexpression assays for CYP17A1, CYP21A2 and CYP19A1 activities.
resultsThe patient presented neonatally with 46,XY DSD and was diagnosed as partial androgen insensitivity syndrome carrying a disease causing AR mutation (p.Q798E). She was raised as a girl and gonadectomized at the age of 4 yr. At 9 yr progressive clitoral enlargement prompted reassessment. Urinary steroid analysis was indicative of POR deficiency, but surprisingly androgen production was normal. Genetic analysis identified compound heterozygous POR mutations (p.601fsX12/p.Y607C). In vitro analysis confirmed p.Y607C as a pathogenic mutation with differential inhibition of steroidogenic CYP enzymes.
conclusionBoth mutant AR and POR are likely to contribute to the neonatal presentation with 46,XY DSD. Virilization at the time of adrenarche appears to suggest an age-dependent, diminishing disruptive effect of both mutant proteins. This case further highlights the importance to assess both gonadal and adrenal function in patients with 46,XY DSD.
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Registered trials
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.