Novel mutations in DAX1 of X-linked adrenal hypoplasia congenita over several generations in one family

Endocr Pract. 2013 Jul-Aug;19(4):e105-11. doi: 10.4158/EP12368.CR.

Abstract

Objective: X-linked adrenal hypoplasia congenital (AHC) is a rare disorder caused by mutations in DAX1 gene. We report a case of X-linked AHC in a large family to analyze the pathogenesis of this rare disease and to add to our clinical knowledge of it.

Methods: We describe 3-year-old boy's clinical features and laboratory test results, as well as the patient's nuclear family members' clinical symptoms, especially those with features of adrenal insufficiency. Genomic deoxyribonucleic acid (DNA) was extracted from the patient's and the family members' peripheral blood leukocytes, and the coding region and promoter region of DAX1 were directly sequenced.

Results: A 3-year-old boy who was diagnosed with X-linked AHC presented with atypical symptoms, and his laboratory test results revealed elevated serum adrenocorticotropic hormone levels (ACTH) and decreased serum cortisol levels. Three novel mutations were detected in the DAX1 coding sequence in this family: a missense mutation (c.376G>A, p.Val126Met), a synonymous mutation (c.498G>A, p.Arg166Arg), and a nonsense mutation (c.1225C>T, p. Gln409X).

Conclusions: This report describes the familial transmission of AHC over several generations and further expands the number of DAX1 mutations reported in the literature. Early diagnosis and prompt treatment of X-linked AHC are important and may provide a good prognosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital / genetics*
  • Child, Preschool
  • DAX-1 Orphan Nuclear Receptor / genetics*
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Male
  • Mutation
  • Pedigree

Substances

  • DAX-1 Orphan Nuclear Receptor
  • NR0B1 protein, human