A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree

J Pediatr Endocrinol Metab. 2013;26(5-6):551-5. doi: 10.1515/jpem-2012-0086.


Patients with DAX-1 gene mutations on chromosome Xp21 usually present with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Yet, neither correlation between the type of mutation and the age of onset of the disease nor mechanism of the mutation on puberty is fully understood. Here, we report a novel non-sense p.Gln208X mutation in the amino terminal domain of the DAX-1 gene observed in a large family with three boys presenting with adrenal manifestations at different ages. Furthermore, two boys developed spontaneous puberty that failed to progress at similar ages, whereas the other boy developed precocious puberty at 10 month of age. The unique structure of the DAX-1 gene may explain this phenotypic variability. However, more studies are needed to understand the role of the DAX-1 gene on development of the adrenal gland and hypothalamus-pituitary-gonadal axis.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • DAX-1 Orphan Nuclear Receptor / genetics*
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Humans
  • Hypogonadism / genetics*
  • Male
  • Pedigree
  • Puberty, Precocious / genetics*


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