• PMID: 16684822
• Gene Name: NR5A1
• Condition: Infertility
• Association: DAX1 mutations were found in 58% (37/64) of 46,XY phenotypic boys referred with adrenal hypoplasia, and in all boys (8/8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure
• Mutation: G35E, R92Q
• Population size: 117
• Population details: 117 patients (88 infancy/childhood onset of steroid biosynthetic defects, metabolic disorders and autoimmune disorders , adult onset group who presented with primary adrenal failure of unknown etiology after puberty)
• Age: <1-70 yrs
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Other associated phenotypes: adrenal failure, hypogonadotropic hypogonadism,

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.

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 2alpha/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. FAU - Lin, Lin AU - Lin L AD - UCL Institute of Child Health and Department of Medicine, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. FAU - Gu, Wen-Xia AU - Gu WX FAU - Ozisik, Gokhan AU - Ozisik G FAU - To, Wing S AU - To WS FAU - Owen, Catherine J AU - Owen CJ FAU - Jameson, J Larry AU - Jameson JL