title: Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.
abstract: We report a 30-year-old female with adrenal unresponsiveness to ACTH. Her clinical features included no adrenal crisis despite poor drug compliance, poor pubic hair development (Tanner stage 2), well-developed breasts (Tanner stage 5), and regular menstrual cycles. Endocrinological data included blood ACTH 1500 pmol/l, cortisol 18 nmol/l, dehydroepiandrosterone sulphate below 0.26 micromol/l, activated renin 0.37 pmol/l, and aldosterone 3.4 nmol/l. Direct sequencing and allele-specific amplification revealed two novel mutations in the ACTH receptor gene. One was transition from guanine to adenine at nucleotide position 1002, resulting in substitution of aspartate for asparagine at codon 103, and the other was transition from cytosine to thymine at nucleotide 1104, leading to substitution of arginine for tryptophan at codon 137. The present findings lend additional credence to the notions that adrenal androgens play an important role in female pubic hair development and that ovarian development takes place independently of adrenarche.
authors.affiliation: Department of Paediatrics, Keio University School of Medicine, Tokyo, Japan. tomishii@mac.com
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Ogata
authors.forename: G
authors.initials: G
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: E I
authors.initials: EI
authors.lastname: Kinoshita
authors.forename: N
authors.initials: N
authors.lastname: Matsuo
mesh_terms: D000307:Adrenal Gland Diseases / Q000235:genetics* / Q000503:physiopathology; D000311:Adrenal Glands / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006197:Hair; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D018043:Receptors, Corticotropin / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D018043:Receptors, Corticotropin; D000324:Adrenocorticotropic Hormone