Journal of Clinical Endocrinology & Metabolism, Vol 81, 2481-2486, Copyright © 1996 by Endocrine Society

ARTICLES

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, J Mason, KC Copeland, SR Kupfer, RA Pagon and ER McCabe
Department of Pediatrics, University of California, Los Angeles School of Medicine 90024, USA.

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.

This article has been cited by other articles:

				N. Valenzuela Evolution of the gene network underlying gonadogenesis in turtles with temperature-dependent and genotypic sex determination Integr. Comp. Biol., October 1, 2008; 48(4): 476 - 485. [Abstract] [Full Text] [PDF]

				L. Lin, W.-X. Gu, G. Ozisik, W. S. To, C. J. Owen, J. L. Jameson, and J. C. Achermann Analysis of DAX1 (NR0B1) and Steroidogenic Factor-1 (NR5A1) in Children and Adults with Primary Adrenal Failure: Ten Years' Experience J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3048 - 3054. [Abstract] [Full Text] [PDF]

				Z. Zhang, P. E. Burch, A. J. Cooney, R. B. Lanz, F. A. Pereira, J. Wu, R. A. Gibbs, G. Weinstock, and D. A. Wheeler Genomic Analysis of the Nuclear Receptor Family: New Insights Into Structure, Regulation, and Evolution From the Rat Genome Genome Res., April 1, 2004; 14(4): 580 - 590. [Abstract] [Full Text] [PDF]

				K. Tajima, A. Dantes, Z. Yao, K. Sorokina, F. Kotsuji, R. Seger, and A. Amsterdam Down-Regulation of Steroidogenic Response to Gonadotropins in Human and Rat Preovulatory Granulosa Cells Involves Mitogen-Activated Protein Kinase Activation and Modulation of DAX-1 and Steroidogenic Factor-1 J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2288 - 2299. [Abstract] [Full Text] [PDF]

				N. Katsumata, M. Ohtake, T. Hojo, E. Ogawa, T. Hara, N. Sato, and T. Tanaka Compound Heterozygous Mutations in the Cholesterol Side-Chain Cleavage Enzyme Gene (CYP11A) Cause Congenital Adrenal Insufficiency in Humans J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3808 - 3813. [Abstract] [Full Text] [PDF]

				R. M. Calvo, M. Asunción, D. Tellería, J. Sancho, J. L. San Millán, and H. F. Escobar-Morreale Screening for Mutations in the Steroidogenic Acute Regulatory Protein and Steroidogenic Factor-1 Genes, and in CYP11A and Dosage-Sensitive Sex Reversal-Adrenal Hypoplasia Gene on the X Chromosome, Gene-1 (DAX-1), in Hyperandrogenic Hirsute Women J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1746 - 1749. [Abstract] [Full Text]

				L. J. BURKE and A. BANIAHMAD Co-repressors 2000 FASEB J, October 1, 2000; 14(13): 1876 - 1888. [Abstract] [Full Text]

				IMAGe, a New Clinical Association of Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4335 - 4340. [Abstract] [Full Text]

				P. Caron, S. Chauvin, S. Christin-Maitre, A. Bennet, N. Lahlou, R. Counis, P. Bouchard, and M.-L. Kottler Resistance of Hypogonadic Patients with Mutated GnRH Receptor Genes to Pulsatile GnRH Administration J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 990 - 996. [Abstract] [Full Text]

				K. Muroya, E.-i. Kinoshita, T. Kamimaki, N. Matsuo, T. Yorifugi, and T. Ogata Deletion mapping and X inactivation analysis of a non-specific mental retardation gene at Xp21.3-Xp22.11 J. Med. Genet., March 1, 1999; 36(3): 187 - 191. [Abstract] [Full Text]

				A. T. Reutens, J. C. Achermann, M. Ito, M. Ito, W.-X. Gu, R. L. Habiby, P. A. Donohoue, S. Pang, P. C. Hindmarsh, and J. L. Jameson Clinical and Functional Effects of Mutations in the DAX-1 Gene in Patients with Adrenal Hypoplasia Congenita J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 504 - 511. [Abstract] [Full Text]

				S. B. Seminara, F. J. Hayes, and W. F. Crowley Jr. Gonadotropin-Releasing Hormone Deficiency in the Human (Idiopathic Hypogonadotropic Hypogonadism and Kallmann's Syndrome): Pathophysiological and Genetic Considerations Endocr. Rev., October 1, 1998; 19(5): 521 - 539. [Abstract] [Full Text]

				M. Peter, M. Viemann, C.-J. Partsch, and W. G. Sippell Congenital Adrenal Hypoplasia: Clinical Spectrum, Experience with Hormonal Diagnosis, and Report on New Point Mutations of the DAX-1 Gene J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2666 - 2674. [Abstract] [Full Text]

				H.-K. Lee, Y.-K. Lee, S.-H. Park, Y.-S. Kim, S. H. Park, J. W. Lee, H.-B. Kwon, J. Soh, D. D. Moore, and H.-S. Choi Structure and Expression of the Orphan Nuclear Receptor SHP Gene J. Biol. Chem., June 5, 1998; 273(23): 14398 - 14402. [Abstract] [Full Text] [PDF]

				J. Nakae, S. Abe, T. Tajima, N. Shinohara, M. Murashita, Y. Igarashi, S. Kusuda, J. Suzuki, and K. Fujieda Three Novel Mutations and a De Novo Deletion Mutation of the DAX-1 Gene in Patients with X-Linked Adrenal Hypoplasia Congenita J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3835 - 3841. [Abstract] [Full Text] [PDF]

				S. Mesiano and R. B. Jaffe Developmental and Functional Biology of the Primate Fetal Adrenal Cortex Endocr. Rev., June 1, 1997; 18(3): 378 - 403. [Abstract] [Full Text]