Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 5 P17

BES2003 Poster Presentations Clinical Case Reports (52 abstracts)

A novel DAX-1 gene mutation with adrenal hypoplasia congenita, differing degrees of hypogonadism and decreased bone mineral density

T Abdalla 1 , A Owen 2 , A Curtis 3 & A Wilton 1


1Department of Diabetes & Endocrinology, Ysbyty Gwynedd, Bangor, UK; 2Department of Clinical Biochemistry, Ysbyty Gwynedd, Bangor, UK; 3Institute of Human Genetics, International Centre for Life, Newcastle Upon Tyne, UK.


Mutations of the DAX-1 gene cause X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. Two half brothers (same mother, different fathers) were diagnosed as having Addison's aged14 years (brother A) and 7 years (brother B). Their mother had haemochromatosis being homozygous for the Cys 282 Tyr mutation of the HFE gene. Both had delayed pubertal development but defaulted from follow up. Brother A re-presented at 29 years of age with infertility. In view of the history and family tree both brothers were examined and investigated.
Brother A: Examination revealed absence of facial and axillary hair. Pubic hair Tanner stage 3 and testicular volume of 4ml. Investigations: testosterone 1.1 nanomols per litre, FSH 13.2 units per litre, LH 1 unit per litre and ferritin 58.6 micrograms per litre. Sperm analysis confirmed azoospermia. Bone mineral density was 0.815 grams per centimetre squared for lumbar spine and 0.825 grams per centimetre squared for femoral neck.
Brother B: Examination revealed sparse facial and axillary hair. Pubic hair Tanner stage 5 and testicular volume 8ml. Investigations: testosterone 15.1 nanomols per litre, FSH 5.8 units per litre, LH 3.4 units per litre and ferritin 147.6 micrograms per ml. Sperm analysis confirmed azoospermia. Bone mineral density 0.856 grams per centimetre squared for lumbar spine and 0.867 per centimetre squared for femoral neck.
DNA analyses: Both were heterozygous for the Cys282 Tyr mutation of the HFE gene and both also exhibited a novel frame shift mutation of the DAX-1 gene with CT deletion in codon 278 replaced by A and insertion of a premature stop codon TGA at codon 371.
These cases demonstrate different phenotype expression in terms of degree of hypogonadism despite the same gene mutation. The decreased bone mineral density is probably due to pubertal delay rather than the achieved level of gonadal development.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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