A novel missense mutation in Dax-1 with an unusual presentation of X-linked adrenal hypoplasia congenita

Ahmad, I. , Paterson, W.F., Lin, L., Adlard, P., Duncan, P. and Donaldson, M.D.C. (2007) A novel missense mutation in Dax-1 with an unusual presentation of X-linked adrenal hypoplasia congenita. Hormone Research, 68(1), pp. 32-37. (doi: 10.1159/000099835)

Abstract

A male presented at age 2.2 years with a 6-week history of intermittent vomiting and hyperpigmentation. Investigations showed salt wasting with hyperkalaemia, a grossly impaired cortisol response to ACTH stimulation, elevated renin and ACTH. Family history revealed that two maternal uncles had died soon after birth. A third uncle failed to thrive during infancy but improved with a course of cortisone, then being untreated until further investigation revealed adrenal insufficiency. A fourth uncle died aged 10 days, with urinary salt loss and hypoplastic adrenal glands at postmortem. Molecular studies on the proband, his mother, maternal grandmother, and surviving uncle showed a novel C to G substitution at nucleotide position 794 (missense mutation T265R) in the DAX1 (NR0B1) gene. The proband has responded well to steroid replacement but has proved sensitive to 9α-fludrocortisone treatment, developing hypertension on a dose of 133 μg/m2/day. At 8.8 years he was noted to have testicular volumes of 4 ml, despite no other evidence of secondary sexual development and prepubertal gonadotrophin levels. Novel features of this family include a novel DAX1 mutation, marked variability in age of presentation, hypertension on ‘standard’ doses of 9α-fludrocortisone and mild testicular enlar

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ahmad, Professor Imran and Donaldson, Dr Malcolm
• Authors: Ahmad, I., Paterson, W.F., Lin, L., Adlard, P., Duncan, P., and Donaldson, M.D.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Hormone Research
• ISSN: 0301-0163
• Published Online: 16 February 2007