title: Identification of novel mutations of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.
abstract: OBJECTIVE
  X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC.
  
  
  METHODS
  Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region.
  
  
  RESULTS
  Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene.
  
  
  CONCLUSIONS
  Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC.
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Young-Lim
authors.initials: YL
authors.lastname: Shin
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kim
authors.forename: Sangwook
authors.initials: S
authors.lastname: Park
authors.forename: Jung-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Changkyu
authors.initials: C
authors.lastname: Oh
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D000307:Adrenal Gland Diseases / Q000151:congenital / Q000235:genetics*; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins