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

W Guo, TP Burris, YH Zhang, BL Huang… - The Journal of …, 1996 - academic.oup.com
W Guo, TP Burris, YH Zhang, BL Huang, J Mason, KC Copeland, SR Kupfer, RA Pagon…
The Journal of Clinical Endocrinology & Metabolism, 1996academic.oup.com
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 …
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.
Oxford University Press