Home A novel DAX-1 (NR0B1) mutation in a boy with X-linked adrenal hypoplasia congenita
Article
Licensed
Unlicensed Requires Authentication

A novel DAX-1 (NR0B1) mutation in a boy with X-linked adrenal hypoplasia congenita

  • Karine Gerster , Claudia Katschnig , Sascha Wyss , Anne Kolly , Patrick Sproll , Anna Biason-Lauber EMAIL logo and Daniel Konrad EMAIL logo
Published/Copyright: October 31, 2017
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 30 Issue 12

Abstract

Background:

X-linked adrenal hypoplasia congenita (AHC) is caused by mutations in DAX-1 (NR0B1) playing a key role in adrenal and reproductive development.

Case presentation:

Herein we report a 2.5-year-old boy who presented with acute adrenal failure. Family history revealed unexplained death in three brothers of the patient’s mother during infancy. Molecular analysis of the DAX-1 gene revealed the presence of a novel hemizygous mutation, c.870C>A in exon 1, leading to the formation of a premature stop codon. The same mutation was identified in the patient’s mother. The truncated mutant protein is most likely misfolded, sequestered in the endoplasmic reticulum and therefore cannot bind to and activate its target DNA sequences in the nucleus.

Conclusions:

DAX-1 mutation must be considered when diagnosis of primary adrenocortical insufficiency is made, especially if there is a history of unexplained death of maternal male relatives.

Keywords: adrenal insufficiency; DAX-1; X-linked adrenal hypoplasia congenital
Corresponding authors: Anna Biason-Lauber, MD, Department of Medicine, Division of Endocrinology, University of Fribourg, Chemin du Musée 5, 1700 Fribourg, Switzerland, Phone: +41 26 300 8534; and Daniel Konrad, MD PhD, Department of Endocrinology and Diabetology, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland, Phone: +41 44 266 73 09, Fax: +41 44 266 79 83
aAnna Biason-Lauber and Daniel Konrad share last authorship.

Acknowledgments

The work was supported by the Swiss National Science Foundation Grant nr. 320030-130645 to A. B-L.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Sikl H. Addison’s disease due to congenital hypoplasia of the adrenals in an infant aged 33 days. J Pathol Bacteriol 1948;60:323.10.1002/path.1700600220Search in Google Scholar PubMed

2. Iyer AK, McCabe ER. Molecular mechanisms of DAX1 action. Mol Genet Metab 2004;83:60–73.10.1016/j.ymgme.2004.07.018Search in Google Scholar PubMed

3. Yu RN, Ito M, Saunders TL, Camper SA, Jameson JL. Role of Ahch in gonadal development and gametogenesis. Nat Genet 1998;20:353–7.10.1038/3822Search in Google Scholar PubMed

4. Bardoni B, Zanaria E, Guioli S, Floridia G, Worley KC, et al. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat Genet 1994;7:497–501.10.1038/ng0894-497Search in Google Scholar PubMed

5. Lin L, Gu WX, Ozisik G, To WS, Owen CJ, et al. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years’ experience. J Clin Endocrinol Metab 2006;91:3048–54.10.1210/jc.2006-0603Search in Google Scholar PubMed PubMed Central

6. Seminara SB, Achermann JC, Genel M, Jameson JL, Crowley WF Jr. X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females. J Clin Endocrinol Metab 1999;84:4501–9.10.1210/jc.84.12.4501Search in Google Scholar PubMed

7. Domenice S, Latronico AC, Brito VN, Arnhold IJ, Kok F, et al. Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene. J Clin Endocrinol Metab 2001;86:4068–71.10.1210/jcem.86.9.7816Search in Google Scholar PubMed

8. Yeste D, Gonzalez-Nino C, Perez de Nanclares G, Perez-Nanclares G, Audi L, et al. ACTH-dependent precocious pseudopuberty in an infant with DAX1 gene mutation. Eur J Pediatr 2009;168:65–9.10.1007/s00431-008-0710-5Search in Google Scholar PubMed

9. Achermann JC, Ito M, Silverman BL, Habiby RL, Pang S, et al. Missense mutations cluster within the carboxyl-terminal region of DAX-1 and impair transcriptional repression. J Clin Endocrinol Metab 2001;86:3171–5.10.1210/jc.86.7.3171Search in Google Scholar PubMed

10. Lalli E, Bardoni B, Zazopoulos E, Wurtz JM, Strom TM, et al. A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita. Mol Endocrinol 1997;11:1950–60.10.1210/mend.11.13.0038Search in Google Scholar PubMed

11. Nakae J, Tajima T, Kusuda S, Kohda N, Okabe T, et al. Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita. J Clin Endocrinol Metab 1996;81:3680–5.10.1210/jcem.81.10.8855822Search in Google Scholar PubMed

12. Peter M, Viemann M, Partsch CJ, Sippell WG. Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J Clin Endocrinol Metab 1998;83:2666–74.10.1210/jcem.83.8.5027Search in Google Scholar PubMed

Received: 2017-7-4
Accepted: 2017-9-25
Published Online: 2017-10-31
Published in Print: 2017-11-27

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Mini Review
  3. Marine-Lenhart syndrome in two adolescents, including one with thyroid cancer: a case series and review of the literature
  4. Original Articles
  5. The role of enterovirus infections in type 1 diabetes in Tunisia
  6. Serum progranulin levels in relation to insulin resistance in childhood obesity
  7. Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype
  8. Etiologies of short stature in a pediatric endocrine clinic in Southern Thailand
  9. Thyroid evaluation of children and adolescents with Williams syndrome in Zhejiang Province
  10. The use of a radiolucent template to improve bone age X-ray quality (BASIC study)
  11. How often are clinicians performing genital exams in children with disorders of sex development?
  12. Efficacy and safety of percutaneous administration of dihydrotestosterone in children of different genetic backgrounds with micropenis
  13. Higher phthalate concentrations are associated with precocious puberty in normal weight Thai girls
  14. Identification of a novel mutation of NR0B1 in a patient with X-linked adrenal hypoplasia and symptomatic treatment
  15. Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China
  16. Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
  17. Case Reports
  18. Diabetic ketoacidosis, hyperuricemia and encephalopathy intractable to regular-dose insulin
  19. A novel DAX-1 (NR0B1) mutation in a boy with X-linked adrenal hypoplasia congenita
  20. High aldosterone and cortisol levels in salt wasting congenital adrenal hyperplasia: a clinical conundrum
  21. A newborn with combined pituitary hormone deficiency developing shock and sludge
  22. Acknowledgment
https://doi.org/10.1515/jpem-2017-0261
Keywords for this article
adrenal insufficiency; DAX-1; X-linked adrenal hypoplasia congenital

Articles in the same Issue

  1. Frontmatter
  2. Mini Review
  3. Marine-Lenhart syndrome in two adolescents, including one with thyroid cancer: a case series and review of the literature
  4. Original Articles
  5. The role of enterovirus infections in type 1 diabetes in Tunisia
  6. Serum progranulin levels in relation to insulin resistance in childhood obesity
  7. Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype
  8. Etiologies of short stature in a pediatric endocrine clinic in Southern Thailand
  9. Thyroid evaluation of children and adolescents with Williams syndrome in Zhejiang Province
  10. The use of a radiolucent template to improve bone age X-ray quality (BASIC study)
  11. How often are clinicians performing genital exams in children with disorders of sex development?
  12. Efficacy and safety of percutaneous administration of dihydrotestosterone in children of different genetic backgrounds with micropenis
  13. Higher phthalate concentrations are associated with precocious puberty in normal weight Thai girls
  14. Identification of a novel mutation of NR0B1 in a patient with X-linked adrenal hypoplasia and symptomatic treatment
  15. Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China
  16. Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
  17. Case Reports
  18. Diabetic ketoacidosis, hyperuricemia and encephalopathy intractable to regular-dose insulin
  19. A novel DAX-1 (NR0B1) mutation in a boy with X-linked adrenal hypoplasia congenita
  20. High aldosterone and cortisol levels in salt wasting congenital adrenal hyperplasia: a clinical conundrum
  21. A newborn with combined pituitary hormone deficiency developing shock and sludge
  22. Acknowledgment
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 21.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2017-0261/html
Scroll to top button