ArticlePituitary2017
Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.
Article in Pituitary, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Fertility and pregnancy in adrenal insufficiency.Endocrine connections · 2024Review
- Approach to the Patient: Diagnosis of Primary Adrenal Insufficiency in Adults.The Journal of clinical endocrinology and metabolism · 2023Article
- Clinical and genetic characteristics of 42 Chinese paediatric patients with X-linked adrenal hypoplasia congenita.Orphanet journal of rare diseases · 2023Article
- Adult‑onset X‑linked adrenal hypoplasia congenita caused by a novel mutation in DAX1/NR0B1: A case report and literature review.Experimental and therapeutic medicine · 2022Article
- Case report: Clinical characteristics and treatment of secondary osteoporosis induced by X-linked congenital adrenal dysplasia.Frontiers in endocrinology · 2022Article
- Case Report: A Novel Truncating Variant ofFrontiers in endocrinology · 2022Article
- X-linked congenital adrenal hypoplasia: a case presentation.BMC endocrine disorders · 2021Article
- Identification and Analysis of a Novel NR0B1 Mutation in Late-Onset Adrenal Hypoplasia Congenita and Hypogonadism.Journal of the Endocrine Society · 2021Article
- An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant inInternational journal of endocrinology · 2021Article
- Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.Human genetics · 2021Review
- Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1/NR0B1 mutation.BMC endocrine disorders · 2020Article
- Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration?Frontiers in endocrinology · 2020Review
- Primary adrenal insufficiency: New genetic causes and their long-term consequences.Clinical endocrinology · 2020Review
- Current Insights Into Adrenal Insufficiency in the Newborn and Young Infant.Frontiers in pediatrics · 2020Review
- Isolated hypoaldosteronism as first sign of X-linked adrenal hypoplasia congenita caused by a novel mutation in NR0B1/DAX-1 gene: a case report.BMC medical genetics · 2019Article
- Analysis ofF1000Research · 2019Review
- Identification and Functional Analysis of SixJournal of the Endocrine Society · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeDAX-1 (NR0B1) is an orphan nuclear receptor, which plays a critical role in development and regulation of the adrenal gland and hypothalamo-pituitary-gonadal axis. Mutations in NR0B1 lead to adrenal hypoplasia congenita (AHC), hypogonadotropic hypogonadism (HH) and azoospermia in men. Presentation is typically with adrenal insufficiency (AI) during infancy or childhood. To date only eight cases/kindreds are reported to have presented in adulthood.
methodsWe describe two new cases of men with DAX-1 mutations who presented in adulthood and who were diagnosed at a large University Hospital.
resultsCase 1 presented with AI at 19 years. At 38 years he was diagnosed with HH. Detailed history revealed a brother diagnosed with AI at a similar age. Sequencing of the DAX-1 (NR0B1) gene revealed a heterozygous c.775T > C substitution in exon 1, which changes codon 259 from serine to proline (p.Ser259Pro). Case 2 was diagnosed with AI at 30 years. Aged 37 years he presented with HH and azoospermia. He was treated with gonadotropin therapy but remained azoospermic. Testicular biopsy showed maturational arrest and hypospermatogenesis. Analysis of the NR0B1 gene showed a heterozygous c.836C > T substitution in exon 1, resulting in a change of codon 279 from proline to leucine (p.Pro279Leu). This change alters the structure of the repression helix domain of DAX-1 and affects protein complex interactions with NR5A family members.
conclusionsWe describe two missense mutations within the putative carboxyl-terminal ligand binding domain of DAX-1, presenting with AHC and HH in adulthood, from a single center. DAX-1 mutations may be more frequent in adults than previously recognized. We recommend testing for DAX-1 mutations in all adults with primary AI and HH or impaired fertility where the etiology is unclear.
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