A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree
-
Erdem Durmaz
,
Afig Berdeli
Abstract
Patients with DAX-1 gene mutations on chromosome Xp21 usually present with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Yet, neither correlation between the type of mutation and the age of onset of the disease nor mechanism of the mutation on puberty is fully understood. Here, we report a novel non-sense p.Gln208X mutation in the amino terminal domain of the DAX-1 gene observed in a large family with three boys presenting with adrenal manifestations at different ages. Furthermore, two boys developed spontaneous puberty that failed to progress at similar ages, whereas the other boy developed precocious puberty at 10 month of age. The unique structure of the DAX-1 gene may explain this phenotypic variability. However, more studies are needed to understand the role of the DAX-1 gene on development of the adrenal gland and hypothalamus-pituitary-gonadal axis.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors have nothing to declare.
References
1. Guo W, Burris TP, McCabe ER. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalmic-pituitary-adrenal/gonadal axis. Biochem Mol Med 1995;56: 8–13.Suche 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.Suche in Google Scholar
3. Verrijn Stuart AA, Ozisik G, de Vroede MA, Giltay JC, Sinke RJ, et al. An amino-terminal DAX1 (NROB1) missense mutation associated with isolated mineralocorticoid deficiency. J Clin Endocrinol Metab 2007;92:755–61.Suche in Google Scholar
4. Calliari LE, Longui CA, Rocha MN, Faria CD, Kochi C, et al. A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita. Genet Mol Res 2007;10:277–83.Suche in Google Scholar
5. 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 DAX-1 gene. J Clin Endocr Metab 2001;89:4068–71.Suche in Google Scholar
6. 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.Suche in Google Scholar
7. 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 congenital. J Clin Endocrinol Metab 1999;84:504–11.Suche in Google Scholar
8. Iyer AK, McCabe ER. Molecular mechanisms of DAX-1 action. Mol Genet Metab 2004;83:60–73.Suche in Google Scholar
9. Jameson JL. Of mice and men: the tale of steroidogenic factor-1. J Clin Endocrinol Metab 2004;89:5927–9.Suche in Google Scholar
10. 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.Suche in Google Scholar
11. Bassett JH, O’Halloran DJ, Williams GR, Beardwell CG, Shalet SM, et al. Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. Clin Endocrinol 1999;50:69–75.Suche in Google Scholar
12. Laissue P, Copelli S, Bergada I, Bergada C, Barrio G, et al. Partial defects in transcriptional activity of two novel DAX-1 mutations in childhood-onset adrenal hypoplasia congenita. Clin Endocrinol 2006;65:681–6.Suche in Google Scholar
13. Peter M, Viemann M, Partsch CJ, Sippell WG. Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutation of the DAX-1 gene. J Clin Endocrinol Metab 1998;83:2666–74.Suche in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Success has many fathers, failure is orphan
- Review Article
- Normosmic idiopathic hypogonadotropic hypogonadism: update on the genetic background and future challenges
- Original Articles
- Temporary brittle bone disease: association with intracranial bleeding
- Asymmetric dimethylarginine (ADMA) and L-arginine levels in children with glycogen storage disease type I
- Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population
- The role of uncoupling protein 2 and 3 genes polymorphism and energy expenditure in obese Indonesian children
- Thyroid dysfunctions of prematurity and their impacts on neurodevelopmental outcome1)
- Frequency of the E23K polymorphism of the KCNJ11 gene in children born small for gestational age and its influence on auxological and metabolic parameters in the prepubertal period
- Reference intervals for serum thyroid hormones in preterm hospitalized infants1)
- The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents
- A risk score for identifying overweight adolescents with dysglycemia in primary care settings1)
- Thyroid function and morphology in overweight and obese children and adolescents in a Chinese population
- Propionic acidaemia: demographic characteristics and complicationsa
- Negative correlation between serum IL-6 level and cardiorespiratory fitness in 10- to 11-year-old boys with increased BMI
- Penile length and genital anomalies in Egyptian male newborns: epidemiology and influence of endocrine disruptors
- Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial
- Characteristics of infants admitted with hypoglycemia to a neonatal unit
- Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents
- The role of FTO genotype on eating behavior in obese Sardinian children and adolescents
- Prevalence of multiple forms of autoimmunity in Egyptian patients with Turner syndrome: relation to karyotype
- A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree
- Patient Reports
- Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism
- Diabetic ketoacidosis with cerebral hemorrhage and alpha coma in an adolescent female
- A novel mutation in thyrotropin (thyroid-stimulating hormone) gene in congenital hypothyroidism
- Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia
- A case of autosomal dominant osteopetrosis type II with a novel TCIRG1 gene mutation
- The interpretation of color – an endocrine cause of skin discoloration mimicking cyanosis
- Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan
- Turner Syndrome and apparent absent uterus: a case report and review of the literature
- 10.1515/jpem-2012-0133
- Vaginal bleeding in a 4-month-old preterm girl: extreme minipuberty mimicking central precocious puberty
- A rare case of isolated Cushing syndrome in a 3-month-old boy
- Letters to the Editors
- Gynecomastia in puberty is usually asymptomatic and regresses spontaneously
- Is endometriosis ultimately the end result of the interplay between interferon-γ (IFN-γ) and the HOXA10 gene network?
- Does treatment with L-selenomethionine reduce thyroid volume in euthyroid children with autoimmune thyroiditis?
- Meetings
- Meetings Calendar
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Success has many fathers, failure is orphan
- Review Article
- Normosmic idiopathic hypogonadotropic hypogonadism: update on the genetic background and future challenges
- Original Articles
- Temporary brittle bone disease: association with intracranial bleeding
- Asymmetric dimethylarginine (ADMA) and L-arginine levels in children with glycogen storage disease type I
- Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population
- The role of uncoupling protein 2 and 3 genes polymorphism and energy expenditure in obese Indonesian children
- Thyroid dysfunctions of prematurity and their impacts on neurodevelopmental outcome1)
- Frequency of the E23K polymorphism of the KCNJ11 gene in children born small for gestational age and its influence on auxological and metabolic parameters in the prepubertal period
- Reference intervals for serum thyroid hormones in preterm hospitalized infants1)
- The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents
- A risk score for identifying overweight adolescents with dysglycemia in primary care settings1)
- Thyroid function and morphology in overweight and obese children and adolescents in a Chinese population
- Propionic acidaemia: demographic characteristics and complicationsa
- Negative correlation between serum IL-6 level and cardiorespiratory fitness in 10- to 11-year-old boys with increased BMI
- Penile length and genital anomalies in Egyptian male newborns: epidemiology and influence of endocrine disruptors
- Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial
- Characteristics of infants admitted with hypoglycemia to a neonatal unit
- Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents
- The role of FTO genotype on eating behavior in obese Sardinian children and adolescents
- Prevalence of multiple forms of autoimmunity in Egyptian patients with Turner syndrome: relation to karyotype
- A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree
- Patient Reports
- Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism
- Diabetic ketoacidosis with cerebral hemorrhage and alpha coma in an adolescent female
- A novel mutation in thyrotropin (thyroid-stimulating hormone) gene in congenital hypothyroidism
- Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia
- A case of autosomal dominant osteopetrosis type II with a novel TCIRG1 gene mutation
- The interpretation of color – an endocrine cause of skin discoloration mimicking cyanosis
- Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan
- Turner Syndrome and apparent absent uterus: a case report and review of the literature
- 10.1515/jpem-2012-0133
- Vaginal bleeding in a 4-month-old preterm girl: extreme minipuberty mimicking central precocious puberty
- A rare case of isolated Cushing syndrome in a 3-month-old boy
- Letters to the Editors
- Gynecomastia in puberty is usually asymptomatic and regresses spontaneously
- Is endometriosis ultimately the end result of the interplay between interferon-γ (IFN-γ) and the HOXA10 gene network?
- Does treatment with L-selenomethionine reduce thyroid volume in euthyroid children with autoimmune thyroiditis?
- Meetings
- Meetings Calendar
