scholarly journals Delayed-onset adrenal hypoplasia congenita and hypogonadotropic hypogonadism caused by a novel mutation in DAX1

2019 ◽  
Vol 48 (2) ◽  
pp. 030006051988215
Author(s):  
Siyue Liu ◽  
Libin Yan ◽  
Xinrong Zhou ◽  
Chen Chen ◽  
Daowen Wang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Molecular Testing ◽  
Delayed Onset ◽  
Adrenal Hypoplasia Congenita ◽  
Congenital Adrenal Hypoplasia ◽  
Translation Start ◽  
Adrenal Hypoplasia ◽  
Relevant Family History ◽  
Mild Clinical Phenotype

In this study, we described a male who presented with delayed-onset adrenal hypoplasia congenita (AHC) and mild hypogonadotropic hypogonadism (HHG) without a relevant family history. A novel mutation in the DAX1 (dosage-sensitive sex reversal, congenital adrenal hypoplasia critical region on the X chromosome, gene 1) gene was shown to cause X-linked AHC and HHG. Genetic analysis revealed a novel nonsense mutation, c.154G > T (p.Glu52Term), in the DAX1 gene. Molecular testing demonstrated that the milder phenotype caused by this mutation was due to expression of a partially functional, amino-truncated DAX1 protein generated from an alternate in-frame translation start site (methionine at codon 83). This unusual case revealed a potential mechanism for a novel mutation that resulted in an unusual delayed-onset mild clinical phenotype. It expands the spectrum of adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

scholarly journals Corticotroph adenoma of the pituitary in a patient with X-linked adrenal hypoplasia congenita due to a novel mutation of the DAX-1 gene

2005 ◽  
Vol 153 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Ernesto De Menis ◽  
Federico Roncaroli ◽  
Vladimiro Calvari ◽  
Valerio Chiarini ◽  
Paolo Pauletto ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Genomic Analysis ◽  
Adrenal Hypoplasia Congenita ◽  
Congenital Adrenal Hypoplasia ◽  
Exon 1 ◽  
Adrenal Hypoplasia ◽  
Acth Secreting ◽  
Design And Methods

Objective: Mutations in the DAX-1 gene result in X-linked congenital adrenal hypoplasia. The classic clinical presentation is primary adrenal insufficiency in early life and hypogonadotropic hypogonadism at the time of expected puberty, but recent data have expanded the phenotypic spectrum of DAX-1 mutations. We report the occurrence of an ACTH-secreting adenoma in a patient with X-linked congenital adrenal hypoplasia. Design and methods: Detailed clinical, radiological and pathological investigation of the pituitary adenoma. Genomic analysis of the DAX-1 gene in the patient and his mother. Results: In this patient, primary adrenal failure had been diagnosed at 3 years of age and, despite replacement therapy, at 30 years of age progressive pigmentation developed and impairment of the visual field followed. ACTH was 24 980 pg/ml and nuclear magnetic resonance disclosed a huge pituitary adenoma. Three transsphenoidal operations and radiotherapy were necessary to remove the tumor mass and control ACTH secretion. Histologically, the adenoma was composed of chromophobic and basophilic neoplastic cells with positive immunostaining for ACTH. Moreover, a novel mutation was found both in the patient and his mother: a 4 bp insertion (AGCG) at nucleotide 259, in exon 1 resulting in a frame shift and premature termination. Conclusions: This case suggests that in adrenal hypoplasia congenita the development of a pituitary adenoma should be considered when a sudden rise of ACTH occurs despite adequate steroid substitution.

scholarly journals A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism

2012 ◽  
Vol 56 (8) ◽  
pp. 496-500 ◽  
Author(s):  
Claudilene Battistin ◽  
Hamilton Cabral de Menezes Filho ◽  
Sorahia Domenice ◽  
Mirian Yumie Nishi ◽  
Thais Della Manna ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Failure To Thrive ◽  
The Novel ◽  
Site Analysis ◽  
Adrenal Hypoplasia Congenita ◽  
Normal Individuals ◽  
Exon 1 ◽  
Adrenal Hypoplasia ◽  
Low Levels

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient. Arq Bras Endocrinol Metab. 2012;56(8):496-500

Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1

2015 ◽  
Vol 28 (9-10) ◽  
Author(s):  
Amaia Rodríguez Estévez ◽  
Gustavo Pérez-Nanclares ◽  
Joaquin Fernández-Toral ◽  
Francisco Rivas-Crespo ◽  
Juan P. López-Siguero ◽  
...  
Keyword(s):  
Molecular Level ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Gene Mutations ◽  
Delayed Puberty ◽  
Salt Wasting ◽  
Adrenal Hypoplasia Congenita ◽  
Intrafamilial Variability ◽  
Adrenal Hypoplasia

AbstractX-linked adrenal hypoplasia congenita (AHC) is caused byTo characterize clinically and at the molecular level a cohort of Spanish patients with AHC.Nine boys (from five families) with AHC were screened forgene mutations were found in all analyzed patients, one of them being novel (p.Gln305*). One patient presented with preserved hypothalamic-pituitary-gonadal axis. Salt-wasting episodes, delayed puberty, and hypogonadotropic hypogonadism were common, although no association was observed between AHC phenotype and genetic mutations. None of the patients has had descendants.AHC phenotype cannot be predicted based on genetic results as there is no definite genotype-phenotype relationship, including intrafamilial variability. Nevertheless, genetic testing for

Identification of a novel mutation of NR0B1 in a patient with X-linked adrenal hypoplasia and symptomatic treatment

2017 ◽  
Vol 30 (12) ◽  
Author(s):  
Jing Yang ◽  
Yuncheng Lv ◽  
Ye Zhou ◽  
Xinhua Xiao
Keyword(s):  
Frameshift Mutation ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Serum Testosterone ◽  
Symptomatic Treatment ◽  
Serum Testosterone Level ◽  
Coding Region ◽  
Rapid Improvement ◽  
Congenital Adrenal Hypoplasia ◽  
Adrenal Hypoplasia

AbstractBackground:X-linked congenital adrenal hypoplasia (X-linked AHC) is characterized by acute onset of primary adrenal insufficiency in infancy or early childhood and hypogonadotropic hypogonadism (HH) at puberty. Mutations inMethods:The entire coding region of theResults:DNA sequencing revealed a missense mutation (c.383-384 insA) in exon 1, which resulted in a novel frameshift mutation, thereby resulting in a truncated protein (p.Leu129 Pro fs*137). The therapeutic trail with an observation period of 20 weeks showed an effective improvement in symptoms of hypogonadism with human chorionic gonadotropin (HCG) administration, including a rapid improvement of serum testosterone level, descending of testicles as well as enlargement of testicles and growth of penis.Conclusions:Our study identified a novel frameshift mutation of the

scholarly journals A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism

2000 ◽  
Vol 105 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Antoine Tabarin ◽  
John C. Achermann ◽  
Dominique Recan ◽  
Véronique Bex ◽  
Xavier Bertagna ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Delayed Onset

Congenital Adrenal Hypoplasia with Hypogonadotropic Hypogonadism

2009 ◽  
pp. 401-401
Author(s):  
Nils Peters ◽  
Martin Dichgans ◽  
Sankar Surendran ◽  
Josep M. Argilés ◽  
Francisco J. López-Soriano ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Congenital Adrenal Hypoplasia ◽  
Adrenal Hypoplasia
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