Reutens, AT;
Achermann, JC;
Ito, M;
Ito, M;
Gu, WX;
Habiby, RL;
Donohoue, PA;
... Jameson, JL; + view all
(1999)
Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita.
The Journal of Clinical Endocrinology & Metabolism
, 84
(2)
504 - 511.
10.1210/jc.84.2.504.
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Abstract
Adrenal hypoplasia congenita (AHC) is an X-linked disorder caused by mutations in a gene referred to as DAX-1. AHC is characterized by adrenal insufficiency and failure to undergo puberty because of hypogonadotropic hypogonadism. The DAX-1 protein is structurally related to orphan nuclear receptors, although it lacks the characteristic zinc finger DNA-binding domain that is highly conserved in other members of this family. In this report, we describe the clinical features and genetic alterations in six families with AHC. These patients reveal the variable clinical presentation of adrenal insufficiency in AHC and underscore the importance of considering this diagnosis. Nonsense mutations that introduce a stop codon were found in three cases (W171X, W171X, Y399X). Frameshift mutations (405delT, 501delA, and 702delC), each of which resulted in a premature stop codon at amino acid 263, were found in the other three families. Three of these mutations (Y399X, 405delT, 702delC) are novel. Using transient gene expression assays to assess DAX-1 function, these mutations were shown to eliminate the ability of DAX-1 to repress the transcription of genes that are stimulated by a related nuclear receptor, steroidogenic factor-1. These studies reveal the variable clinical presentation of DAX-1 mutations and emphasize the value genetic testing in boys with primary adrenal insufficiency and suspected X-linked AHC.
| Type: | Article |
|---|---|
| Title: | Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1210/jc.84.2.504 |
| Publisher version: | http://dx.doi.org/10.1210/jc.84.2.504 |
| Language: | English |
| Additional information: | © 1999 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: | RECEPTOR STEROIDOGENIC FACTOR-1, HYPOGONADOTROPIC HYPOGONADISM, NUCLEAR RECEPTOR, JAPANESE PATIENTS, GLYCEROL KINASE, KEY REGULATOR, GONADAL AXIS, EXPRESSION, DEFICIENCY, XP21 |
| 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 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/154637 |
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