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Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: Ten years' experience

Lin, L; Gu, WX; Ozisik, G; To, WS; Owen, CJ; Jameson, JL; Achermann, JC; (2006) Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: Ten years' experience. The Journal of Clinical Endocrinology & Metabolism , 91 (8) 3048 - 3054. 10.1210/jc.2006-0603. Green open access

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Abstract

Context: Primary adrenal failure is a life-threatening condition that can be caused by a range of etiologies, including autoimmune, metabolic, and developmental disorders. The nuclear receptors DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) play an important role in adrenal development and function, and mutations in these transcription factors have been found in patients with adrenal hypoplasia.Objective: Our objective was to investigate the prevalence of DAX1 and SF1 mutations in children and adults with primary adrenal failure of unknown etiology (i.e. not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, or autoimmune disease).Patients: One hundred seventeen patients were included. Eighty-eight individuals presented in infancy or childhood with adrenal hypoplasia or primary adrenal failure of unknown etiology (n = 64 46, XY phenotypic males; n = 17 46, XY gonadal dysgenesis/ impaired androgenization; n = 7 46, XX females). Twenty-nine individuals presented in adulthood with Addison's disease of unknown etiology.Methods: Mutational analysis of DAX1 ( NR0B1) ( including exon 2 alpha/1A) and SF1 ( NR5A1) was done by direct sequencing.Results: DAX1 mutations were found in 58% ( 37 of 64) of 46, XY phenotypic boys referred with adrenal hypoplasia and in all boys ( eight of eight) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found in only two patients with 46, XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group.Conclusions: DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys. SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46, XY individuals.

Type: Article
Title: Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: Ten years' experience
Open access status: An open access version is available from UCL Discovery
DOI: 10.1210/jc.2006-0603
Publisher version: http://dx.doi.org/10.1210/jc.2006-0603
Language: English
Additional information: © 2006 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: XY SEX REVERSAL, HYPOPLASIA CONGENITA, HYPOGONADOTROPIC HYPOGONADISM, NUCLEAR RECEPTOR, GONADAL DEVELOPMENT, NONSENSE MUTATION, IMAGE ASSOCIATION, 46,XY PATIENT, GENE, INSUFFICIENCY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/153190
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