A novel mutation in the NR0B1 (DAX1) gene in a large family with two boys affected by congenital adrenal hypoplasia

Rojek, Aleksandra; Flader, Maciej; Małecka, Elżbieta; Niedziela, Marek

doi:10.14310/horm.2002.1495

Cited by 4 publications

(5 citation statements)

References 21 publications

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“…Primary adrenal insufficiency is a potentially life threatening disorder that can present with salt losing crisis or profound hypoglycemia and requires urgent resuscitation and appropriate steroid replacement. 2 Primary adrenal insufficiency can occur at any age, in the neonatal period, in infancy or in childhood 6. It is difficult to diagnose AHC in a neonate because it is often misdiagnosed as the salt wasting form of congenital adrenal hyperplasia which is the most common etiology for adrenal insufficiency in this age group 2,4.…”

Section: Discussionmentioning

confidence: 99%

Adrenal hypoplasia congenita in identical twins

Amer

Rubaya

Alzahrani

2019

SMJ

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We are presenting a monozygotic twin brothers presented at different ages with different presentations. Twin-A presented at age of 18 days with salt losing crisis. Investigations revealed high plasma renin with low-normal aldosterone. Adrenocorticotropic hormone stimulation test revealed low 17-OH progesterone at 0 and 60 minutes. Adrenocorticotropic hormone level and serum cortisol were normal, which excluded initial impression of congenital adrenal hyperplasia. He was diagnosed to have isolated primary hypoaldosteronism. At age of 18 months, he was noticed to have hyperpigmentation of lips and gum. Adrenal failure was suspected, and hydrocortisone was added. Twin-B presented at 9 years and 6 months of age with adrenal crisis. Both were having unilateral undescended testis. Adrenal hypoplasia congenita (AHC) was suspected after his twin’s presentation. Molecular analysis for gene study for both of them revealed adrenal insufficiency, NR0B1 (DAX1) gene mutation. In conclusion, gene analysis is important for the diagnosis of AHC and for genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Adrenal hypoplasia congenita in identical twins

Amer

Rubaya

Alzahrani

2019

SMJ

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“…Most patients with X-linked AHC present adrenal insufficiency early in life and have combined glucocorticoid and mineralocorticoid deficiency [ 32 ]. AHC is also characterized by puberty failure and hypogonadotropic hypogonadism as well as growth hormone deficiency later in life [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

X-Linked Adrenal Hypoplasia Congenita in a Boy due to a Novel Deletion of the EntireNR0B1 (DAX1)andMAGEB1–4Genes

Rojek

Krawczyński

Jamsheer

et al. 2016

International Journal of Endocrinology

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X-linked Adrenal Hypoplasia Congenita (AHC) is caused by deletions or point mutations in the NR0B1 (DAX1) gene. We present a boy with AHC who came at the age of 25 days in a severe state due to prolonged vomiting and progressive dehydration. Laboratory studies showed prominent hyponatremia and hyperkaliemia but not hypoglycemia. Primary adrenal insufficiency was confirmed with low serum cortisol levels and high plasma ACTH levels. Hydrocortisone therapy combined with saline and glucose infusions was started immediately after blood collection. Two exons of the NR0B1 (DAX1) gene were impossible to amplify using the standard PCR method. Array CGH was used to confirm the putative copy-number variation of NR0B1 (DAX1) revealing a novel hemizygous deletion encompassing the entire NR0B1 (DAX1) gene together with the MAGEB genes. This genetic defect was also present in heterozygosity in the patient's mother. We show that NR0B1 (DAX1) gene analysis is important for confirmation of AHC diagnosis and highlights the role of genetic counseling in families with AHC patients, particularly those with X chromosome microdeletions, covering more than NR0B1 (DAX1) alone. We hope that further clinical follow-up of this patient and his family will shed a new light on the role of MAGEB genes.

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“…More than 200 different mutations in the DAX1 gene have been identified to date, but the relationship between mutations and the phenotype of AHC has not been documented (23). The age of onset of adrenal insufficiency, disease severity, and clinical symptoms could vary despite carrying the same mutation (24). It is probable that epigenetic or non-genetic mechanisms could modulate patients' phenotype in X-linked AHC.…”

Section: Genetic Causes For Pai Case Seriesmentioning

confidence: 99%

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

Gao

Chen

2020

Front. Pediatr.

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Primary adrenocortical insufficiency (PAI) is an important cause of morbidity in neonates. The most common cause of PAI in neonates is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). Other rarer monogenic cases, for example, adrenal hypoplasia congenita (AHC) or familial glucocorticoid deficiency, also simulate clinical manifestation of 21-OHD, leading to misdiagnosis. The therapies and prognosis of these monogenic cases of PAI are entirely different. This study aimed to compare the differences of clinical data and identify genetic etiologies of PAI cases in the neonatal period. All 7 neonates initially presented with hyperpigmentation, hyponatremia, hyperkalemia, and high serum adrenocorticotropic hormone levels. Only CAH patients showed hyperandrogenism and remarkably elevated serum 17-hydroxyprogesterone levels. All the pathogenic mutations found in CYP21A2 were well known, except c.1069C>T (exon 8). The male patient with AHC had a novel hemizygous deletion of exon 2 in DAX1. The other one with familial glucocorticoid deficiency type 1 had two novel heterozygous mutations in the gene coding melanocortin 2 receptor, c.701C>T (exon 2) and c.119delT (exon 2). Glucocorticoid and/or mineralocorticoid replacement therapy depends on the cause of PAI. Genetic testing can be performed as a alternative diagnostic approach to provide information about therapy, prognosis, and genetic counseling.

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A novel mutation in the NR0B1 (DAX1) gene in a large family with two boys affected by congenital adrenal hypoplasia

Cited by 4 publications

References 21 publications

Adrenal hypoplasia congenita in identical twins

Adrenal hypoplasia congenita in identical twins

X-Linked Adrenal Hypoplasia Congenita in a Boy due to a Novel Deletion of the EntireNR0B1 (DAX1)andMAGEB1–4Genes

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

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