Salvi, R;
Gomez, F;
Fiaux, M;
Schorderet, D;
Jameson, JL;
Achermann, JC;
Gaillard, RC;
(2002)
Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1.
The Journal of Clinical Endocrinology & Metabolism
, 87
(9)
4094 - 4100.
10.1210/jc.2001-011930.
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Abstract
DAX-1 [dosage-sensitive sex reversal, adrenal hypoplasia congenital (AHC) critical region on the X chromosome, gene 11 is a transcription factor expressed in the adrenal gland and at all levels of the gonadotrope axis. Inactivating mutations of DAX1 result in the X-linked form of AHC with associated hypogonadotropic hypogonadism. AHC usually reveals itself as adrenal failure in early infancy, although a wide range of phenotypic expression has been reported. We describe a patient who was diagnosed with adrenal failure at 6 wk of age, but who experienced recovery of adrenal function of several months' duration later in infancy. He subsequently failed to undergo puberty because of hypogonadotropic hypogonadism of pituitary origin, and he was also diagnosed with schizophrenia in early adulthood. Molecular genetic analyses revealed a complex rearrangement in DAX1, including a 2.2-kb deletion spanning the entire second exon and a small 27-bp insertion. The putative protein encoded by this mutated gene is 429 amino acids long. The initial 389 residues probably correspond to the wild-type DAX-1 sequence, whereas the last 40 amino acids are presumably completely unrelated, being transcribed from the intronic sequence adjacent to exon 1. In vitro functional analyses confirm the absence of repressor activity exerted by such mutant protein. These studies expand the genotypic and phenotypic spectrum of DAX-1 insufficiency in humans.
| Type: | Article |
|---|---|
| Title: | Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1210/jc.2001-011930 |
| Publisher version: | http://dx.doi.org/10.1210/jc.2001-011930 |
| Language: | English |
| Additional information: | © 2002 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: | HYPOPLASIA CONGENITA, HYPOGONADOTROPIC HYPOGONADISM, TRANSCRIPTIONAL REPRESSION, SEX DETERMINATION, MUTATIONS, EXPRESSION, HORMONE, DIAGNOSIS, DOMAIN, AXIS |
| 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 > 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/95067 |
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