scholarly journals An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Samira Kalayinia ◽  
Saeed Talebi ◽  
Mohammad Miryounesi ◽  
Peymaneh Sarkhail ◽  
Nejat Mahdieh
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Point Mutations ◽  
In Silico Analysis ◽  
Cyp21a2 Gene ◽  
Large Deletions ◽  
Congenital Adrenal Hypoplasia ◽  
Novel Variant ◽  
Adrenal Hypoplasia ◽  
Hydroxy Progesterone ◽  
High Level

X-linked congenital adrenal hypoplasia due to NR0B1 mutation is characterized by hypogonadotropic hypogonadism (HH) and infertility. Here, we describe a novel pathogenic frameshift variant in NR0B1 associated with congenital adrenal hypoplasia by whole exome sequencing in an Iranian case with high level of testosterone. Clinical evaluations and pedigree drawing were performed. Point mutations, gene conversions, and large deletions of the CYP21A2 gene were checked. WES and segregation analyses were conducted. In silico analysis was also performed for the novel variant. The ACTH, 17-hydroxy progesterone c, and DHEA sulfate values were elevated up to 624.6 pg/mL, 8.6 pmol/L, and 17.8UMOL/L, respectively. No mutation was found in the CYP21A2 gene. WES identified a novel hemizygous frameshift insertion c.218_219insACCA: p.His73GlnfsTer41 variant in the NR0B1 gene with a pathogenic effect according to ACMG criteria. Genetic testing is helpful for differential diagnosis in primary adrenal insufficiency disorders. NR0B1 may be a common cause of congenital adrenal hypoplasia in our population.

scholarly journals Congenital Adrenal Hypoplasia: Clinical Spectrum, Experience with Hormonal Diagnosis, and Report on New Point Mutations of the DAX-1 Gene

1998 ◽  
Vol 83 (8) ◽  
pp. 2666-2674 ◽  
Author(s):  
Michael Peter ◽  
Matthias Viemann ◽  
Carl-Joachim Partsch ◽  
Wolfgang G. Sippell
Keyword(s):  
Muscular Dystrophy ◽  
Hypogonadotropic Hypogonadism ◽  
Point Mutations ◽  
Salt Wasting ◽  
Young Infants ◽  
Congenital Adrenal Hypoplasia ◽  
Contiguous Gene ◽  
Adrenal Hypoplasia ◽  
Duchenne's Muscular Dystrophy ◽  
Cortisol Deficiency

abstract X-linked congenital adrenal hypoplasia (AHC) is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the DAX-1 gene, a recently discovered member of the nuclear hormone receptor superfamily. Hypogonadotropic hypogonadism is frequently associated with AHC. AHC occurs as part of a contiguous gene syndrome together with glycerol kinase deficiency (GKD) and Duchenne’s muscular dystrophy. The present series, collected over the past 2 decades, includes 18 AHC boys from 16 families: 4 with AHC, GKD, and Duchenne’s muscular dystrophy; 2 with AHC and GKD; and 12 with AHC (5 young adults with hypogonadotropic hypogonadism). Most of the boys presented with salt wasting and hyperpigmentation during the neonatal period. Plasma steroid determinations performed in the first weeks of life often showed confusing results, probably caused by steroids produced in the neonates’ persisting fetocortex. Aldosterone deficiency usually preceded cortisol deficiency, which explains why the patients more often presented with salt-wasting rather than with hypoglycemic symptoms. An ACTH test was often necessary to detect cortisol deficiency in the very young infants. In some patients, serial testing was necessary to establish the correct diagnosis. In 4 boys studied during the first 3 months after birth, we found pubertal LH, FSH, and testosterone plasma levels indicating postnatal transient activation of the hypothalamic-pituitary-gonadal axis as in normal boys. Previous studies have shown that the DAX-1 gene is deleted in the AHC patients with a contiguous gene syndrome and is mutated in nondeletion patients. Most of the point mutations identified in AHC patients were frameshift mutations and stop mutations. In the 15 patients available for molecular analysis of the DAX-1 gene, there were large deletions in 6 patients and point mutations in another 7 patients. All of the point mutations identified in the present study resulted in a nonfunctional truncated DAX-1 protein. Two brothers with primary adrenal insufficiency and a medical history that strongly suggested AHC had no mutation in the DAX-1 gene. Thus, additional, as yet unknown genes must play a part in normal adrenal cortical development.

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

scholarly journals Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism

2012 ◽  
Vol 56 (8) ◽  
pp. 540-544 ◽  
Author(s):  
Daiane Beneduzzi ◽  
Ericka B. Trarbach ◽  
Ana Claudia Latronico ◽  
Berenice Bilharinho de Mendonca ◽  
Letícia F. G. Silveira
Keyword(s):  
In Silico ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
In Silico Analysis ◽  
Control Group ◽  
Coding Region ◽  
Novel Variant ◽  
Gonadotropin Releasing Hormone Receptor ◽  
Inactivating Mutation ◽  
Silico Analysis

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.[Asn10Lys;Gln11Lys]; [Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed that the previously described p.Asn10Lys and p.Gln11Lys are in the same allele, in compound heterozygozity with the novel variant p.Tyr283His. The p.[Asn10Lys;Gln11Lys] are known inactivating mutations. The p.Tyr283His affects a well-conserved residue, and in silico analysis suggested it is a deleterious variant. We describe a novel GNRHR mutation in a male with nIHH. Absence of the mutation in the control group, conservation among species, in silico analysis, and familial segregation suggest that p.Tyr283His, which was identified in compound heterozygozity with the p.[Asn10Lys;Gln11Lys] variants, is an inactivating mutation. Arq Bras Endocrinol Metab. 2012;56(8):540-4

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 Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation

2011 ◽  
Vol 26 (3) ◽  
pp. 724-728 ◽  
Author(s):  
C. Frapsauce ◽  
C. Ravel ◽  
M. Legendre ◽  
M. Sibony ◽  
J. Mandelbaum ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Congenital Adrenal Hypoplasia ◽  
Adrenal Hypoplasia

scholarly journals Resistance Levels and rpoB Gene Mutations among In Vitro-Selected Rifampin-Resistant Mycobacterium tuberculosis Mutants

2006 ◽  
Vol 50 (8) ◽  
pp. 2860-2862 ◽  
Author(s):  
Emma Huitric ◽  
Jim Werngren ◽  
Pontus Juréen ◽  
Sven Hoffner
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Point Mutations ◽  
Gene Mutations ◽  
Rpob Gene ◽  
Clinical Isolates ◽  
Large Deletions ◽  
High Level ◽  
Level Resistance

ABSTRACT The distribution and resistance levels of 189 in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants of Beijing and other genotypes were determined. Apart from a higher amount of codon 522 point mutations and large deletions, a spread of mutations similar to that reported for clinical isolates was seen. Most mutations were correlated with high-level resistance; a lower level, or a MIC of <16 mg/liter, was associated with codon 522 mutations. Multiple mutations were detected in two Beijing mutants.

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

Congenital adrenal hypoplasia and hypogonadotropic hypogonadism: Phenotypic variability of the DAX-1 gene R267P mutation

2012 ◽  
Vol 59 (2) ◽  
pp. 140-142
Author(s):  
Myriam Sánchez-Pacheco ◽  
Oscar Moreno-Pérez ◽  
Ruth Sánchez-Ortiga ◽  
Antonio Picó ◽  
Francisca Moreno
Keyword(s):  
Phenotypic Variability ◽  
Hypogonadotropic Hypogonadism ◽  
Congenital Adrenal Hypoplasia ◽  
Adrenal Hypoplasia
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