A novel DAX-1 mutation in two male siblings presenting with precocious puberty and late-onset hypogonadotropic hypogonadism
-
Yanxia Liu
,
Jinlei Yuan
Abstract
Background
The DAX-1 gene is associated with X-linked adrenal hypoplasia congenita (AHC). Our objective was to compare the DAX-1 gene sequence of two male siblings exhibiting different clinical manifestations of AHC.
Methods
Clinical features were analyzed and laboratory data were collected from both siblings. Genomic DNA was extracted from the peripheral blood leukocytes of the siblings and their parents and the DAX-1 gene exons and intron-flanking regions were amplified by the polymerase chain reaction. The DAX-1 gene sequences were compared following sequencing.
Results
AHC was diagnosed based on a comprehensive review of the clinical presentation and laboratory tests. Gene analysis revealed a nonsense mutation in DAX-1 gene exon 1 (c.192C>G), resulting in a premature termination codon and a truncated 64-amino acid protein product (p.Tyr64X).
Conclusions
Our report provides evidence that defined point mutations in the DAX-1 gene do not necessarily translate into the same clinical manifestations of AHC, even in patients with the same pedigree.
Acknowledgments
We thank all the authors for taking responsibility of making this submission of the manuscript successful with their valuable inputs from time to time.
Author contributions: Yanxia Liu and Jinlei Yuan carried out the experiment work and the data collection, Yanxia Liu drafted the manuscript, Yanyan Jiang participated in the design and acquisition of data, Huijuan Zhang and Guijun Qin carried out the study design and the analysis. All authors read and approved the final manuscript.
Research funding: Young Foundation of the First Affiliated Hospital of Zhengzhou University (2013).
Employment or leadership: None declared.
Honorarium: None declared.
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. Muscatelli F, Strom TM, Walker AP, Zanaria E, Recan D, et al. Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature 1994;372:672–6.10.1038/372672a0Search in Google Scholar
2. Zanaria E, Muscatelli F, Bardoni B, Strom TM, Guioli S, et al. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 1994;372:635–41.10.1038/372635a0Search in Google Scholar
3. Reutens AT, Achermann JC, Ito M, Ito M, Gu WX, et al. Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita. J Clin Endocrinol Metab 1999;84:504–11.10.1210/jc.84.2.504Search in Google Scholar
4. Yu RN, Achermann JC, Ito M, Jameson JL. The role of DAX-1 in reproduction. Trends Endocrinol Metab 1998;9:169–75.10.1016/S1043-2760(98)00048-4Search in Google Scholar
5. Ho J, Zhang YH, Huang BL, McCabe ER. NR0B1A: an alternatively spliced form of NR0B1. Mol Genet Metab 2004;83:330–6.10.1016/j.ymgme.2004.10.002Search in Google Scholar PubMed
6. Guo W, Burris TP, Mc Cabe ER. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis. Biochem Mol Med 1995;56:8–13.10.1006/bmme.1995.1049Search in Google Scholar PubMed
7. Yang F, Hanaki K, Kinoshita T, Kawashima Y, Nagaishi J, et al. Late-onset adrenal hypoplasia congenital caused by a novel mutation of the DAX-1 gene. Eur J Pediatr 2009;168:329–31.10.1007/s00431-008-0779-xSearch in Google Scholar PubMed
8. Wang D, Chen C, Liu Y, Wang L, Li X. One case of late-onset adrenal hypoplasia congenital caused by a novel mutation of the DAX-1 gene. Chin J Endocrinol Metab 2011;27:47–9.Search in Google Scholar
9. De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, et al. 21-Hydroxylase deficiency: classical and nonclassical congenital adrenal hyperplasia. Source endotext (internet). South Dartmouth (MA): MDText.com, Inc, 2000.Search in Google Scholar
10. Suntharalingham JP, Buonocore F, Duncan AJ, Achermann JC. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best Pract Res Clin Endocrinol Metab 2015;29:607–19.10.1016/j.beem.2015.07.004Search in Google Scholar PubMed PubMed Central
11. Tabarin A, Achermann JC, Recan D, Bex V, Bertagna X, et al. P. A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. J Clin Invest 2000;105:321–8.10.1172/JCI7212Search in Google Scholar PubMed PubMed Central
12. Marilus R, Dickerman Z, Kaufman H, Varsano I, Laron Z. Addison’s disease associated with precocious sexual development in a boy. Acta Paediatr Scand 1981;70:587–9.10.1111/j.1651-2227.1981.tb05748.xSearch in Google Scholar PubMed
13. Koh JW, Kang SY, Kim GH, Yoo HW, Yu J. Central precocious puberty in a patient with X-linked adrenal hypoplasia congenita and Xp21 contiguous gene deletion syndrome. Ann Pediatr Endocrinol Metab 2013;18:90–4.10.6065/apem.2013.18.2.90Search in Google Scholar PubMed PubMed Central
14. Darcan S, Goksen D, Ozen S, Ozkinay F, Durmaz B, et al. Gonadotropin-dependent precocious puberty in a patient with X-linked adrenal hypoplasia congenita caused by a novel DAX-1 mutation. Horm Res Paediatr 2011;75:153–6.10.1159/000320701Search in Google Scholar PubMed
15. Domenice S, Latronico AC, Brito IN, 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
16. Durmaz E, Turkkahraman D, Berdeli A, Atan M, Karaguzel G, et al. A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree. J Pediatr Endocrinol Metab 2013;26:551–5.10.1515/jpem-2012-0086Search in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Adrenocortical neoplasms in adulthood and childhood: distinct presentation. Review of the clinical, pathological and imaging characteristics
- Original Articles
- Assessment of health-related quality of life in Egyptian adolescents with type 1 diabetes: DEMPU survey
- Non-HDL-cholesterol and C-reactive protein in children and adolescents with type 1 diabetes
- Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients
- Vascular risk factors are associated with retinal arteriolar narrowing and venular widening in children and adolescents with type 1 diabetes
- Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe?
- Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening
- Resting energy expenditure in girls with Turner syndrome
- AMH levels in girls with various pubertal problems
- Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?
- Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism
- A novel DAX-1 mutation in two male siblings presenting with precocious puberty and late-onset hypogonadotropic hypogonadism
- Case Reports
- Adrenarche unmasks compound heterozygous 3β-hydroxysteroid dehydrogenase deficiency: c.244G>A (p.Ala82Thr) and the novel 931C>T (p.Gln311*) variant in a non-salt wasting, severely undervirilised 46XY
- Three cases of Gordon syndrome with dominant KLHL3 mutations
- Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome
Articles in the same Issue
- Frontmatter
- Review
- Adrenocortical neoplasms in adulthood and childhood: distinct presentation. Review of the clinical, pathological and imaging characteristics
- Original Articles
- Assessment of health-related quality of life in Egyptian adolescents with type 1 diabetes: DEMPU survey
- Non-HDL-cholesterol and C-reactive protein in children and adolescents with type 1 diabetes
- Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients
- Vascular risk factors are associated with retinal arteriolar narrowing and venular widening in children and adolescents with type 1 diabetes
- Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe?
- Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening
- Resting energy expenditure in girls with Turner syndrome
- AMH levels in girls with various pubertal problems
- Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?
- Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism
- A novel DAX-1 mutation in two male siblings presenting with precocious puberty and late-onset hypogonadotropic hypogonadism
- Case Reports
- Adrenarche unmasks compound heterozygous 3β-hydroxysteroid dehydrogenase deficiency: c.244G>A (p.Ala82Thr) and the novel 931C>T (p.Gln311*) variant in a non-salt wasting, severely undervirilised 46XY
- Three cases of Gordon syndrome with dominant KLHL3 mutations
- Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome
