Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism

J Clin Endocrinol Metab. 1996 Jul;81(7):2481-6. doi: 10.1210/jcem.81.7.8675564.

Abstract

The gene responsible for X-linked adrenal hypoplasia congenita, DAX1, encodes a member of the nuclear hormone receptor superfamily. We sequenced 8851 bp that contained the DAX1 genomic region. The DAX gene was composed of two exons and one 3.4-kilobase intron. Putative TATA and GC boxes and a putative steroidogenic factor 1 response element were present in the 5'-flanking region. Two potentially polymorphic short tandem repeats were identified. The first exon encoded two putative novel zinc finger motifs within a putative DNA binding domain and part of the ligand binding domain, and the second exon encoded the remainder of the ligand binding domain. Although the putative DNA binding domain of DAX1 does not contain substantial sequence similarity to other nuclear hormone receptor superfamily members, the putative ligand binding domain had remarkable similarity to other family members. Single-strand conformational polymorphism analysis permitted identification of three new mutations in DAX1. In conclusion, single-strand conformational polymorphism analysis facilitates identification of mutations in the DAX1 gene, and the short tandem repeats may permit linkage analysis in families in which mutations are not yet identified. We speculate that DAX1 may be the most primitive member of the nuclear hormone receptor superfamily identified in mammals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Insufficiency / congenital
  • Adrenal Insufficiency / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / genetics*
  • Deoxyribonuclease EcoRI
  • Exons
  • Female
  • Genetic Linkage
  • Humans
  • Hypogonadism / genetics*
  • Introns
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic
  • Receptors, Retinoic Acid / genetics*
  • Repressor Proteins*
  • Sequence Analysis, DNA*
  • Steroidogenic Factor 1
  • Transcription Factors / genetics*
  • X Chromosome*

Substances

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • NR0B1 protein, human
  • NR5A1 protein, human
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Steroidogenic Factor 1
  • Transcription Factors
  • Deoxyribonuclease EcoRI

Associated data

  • GENBANK/U31929