Document Detail

A novel missense mutation in DAX-1 with an unusual presentation of X-linked adrenal hypoplasia congenita.
MedLine Citation:
PMID:  17308433     Owner:  NLM     Status:  MEDLINE    
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 9alpha-fludrocortisone treatment, developing hypertension on a dose of 133 microg/m(2)/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 9alpha-fludrocortisone and mild testicular enlargement.
Imran Ahmad; Wendy F Paterson; Lin Lin; Peter Adlard; Philippa Duncan; John Tolmie; John C Achermann; Malcolm D C Donaldson
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2007-02-16
Journal Detail:
Title:  Hormone research     Volume:  68     ISSN:  1423-0046     ISO Abbreviation:  Horm. Res.     Publication Date:  2007  
Date Detail:
Created Date:  2007-06-08     Completed Date:  2007-08-13     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0366126     Medline TA:  Horm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  32-7     Citation Subset:  IM    
Copyright Information:
Copyright 2007 S. Karger AG, Basel.
Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK.
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MeSH Terms
Adrenal Glands / abnormalities*,  physiopathology
Adrenal Insufficiency / congenital*,  drug therapy,  physiopathology
Anti-Inflammatory Agents / therapeutic use
Child, Preschool
Cortisone / adverse effects,  analogs & derivatives
DAX-1 Orphan Nuclear Receptor
DNA Mutational Analysis
DNA-Binding Proteins / genetics*,  physiology
Genetic Diseases, X-Linked / drug therapy,  physiopathology*
Hydrocortisone / therapeutic use
Mutation, Missense
Receptors, Retinoic Acid / genetics*,  physiology
Repressor Proteins / genetics*,  physiology
Testis / physiopathology*
Grant Support
079666//Wellcome Trust
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/DAX-1 Orphan Nuclear Receptor; 0/DNA-Binding Proteins; 0/NR0B1 protein, human; 0/Receptors, Retinoic Acid; 0/Repressor Proteins; 50-23-7/Hydrocortisone; 53-06-5/Cortisone; 79-60-7/9-fluorocortisone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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