Dataset Information

Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.

ABSTRACT: DAX-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.We describe two new cases of men with DAX-1 mutations who presented in adulthood and who were diagnosed at a large University Hospital.Case 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.We 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.

SUBMITTER: Kyriakakis N

PROVIDER: S-EPMC5606946 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.

Kyriakakis Nikolaos N Shonibare Tolulope T Kyaw-Tun Julie J Lynch Julie J Lagos Carlos F CF Achermann John C JC Murray Robert D RD

Pituitary 20171001 5

<h4>Purpose</h4>DAX-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.<h4>Methods</h4>We describe two n ...[more]

PMID: 28741070

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Project description:Background: Adrenal myelolipoma (AML) is a nonfunctional benign neoplasm from the adrenal cortex, composed of mature fat and hematopoietic tissue. Usually, patients have no symptoms. However, some patients with hypertension and blood pressure normalize after AML surgery, indicating some connections between AML and hypertension. Materials and Methods: This was a retrospective cohort study of 369 patients diagnosed with AML from September 2008 to December 2018 collected in the Urology Department of West China Hospital, Chengdu, Sichuan, China. We collected clinical records of patients before surgery. Postoperative follow-up was also carried out for those with hypertension and whether patients needed to take antihypertensive drugs and postoperative blood pressure were recorded. We aim to explore the characteristics of both patients with AML having hypertension and having remission of hypertension in 1 year after surgery. Results: There were 369 patients with AML included in the study, 156 men and 213 women, aged 49.86 ± 11.61 years old. Among them, 121 (32.8%) patients presented with hypertension. Body mass index was significantly higher in the hypertension group than that in the nonhypertension group, even after adjusting other variables (26.26 ± 3.43 vs. 24.28 ± 3.38 kg/m2, P < 0.001 for both univariate and multivariate analyses). Sixty patients were followed up for 1-9 years, with a median follow-up of 52 months. The duration of hypertension in the remission group was shorter than that in the non-remission group (P = 0.020), and the tumor lateralization was significantly different between the two groups (P = 0.005). Conclusions: Nearly one-third of patients with AML suffered from hypertension in our study, and there existed some potential links between AML and hypertension. To be more specific, AML-related hypertension was more likely to result from obesity and renal compression by perirenal fat than from endocrine disorders or blood vessels compression. Patients with AML and with more than 3 years of hypertension might have less possibility to recover.

Dataset Information

Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.

Publications

Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.

Similar Datasets

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