scholarly journals Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome

2018 ◽  
Vol 89 (5) ◽  
pp. 352-361 ◽  
Author(s):  
Walter L. Miller ◽  
Deborah P. Merke
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Matrix Protein ◽  
Connective Tissue Disorder ◽  
Joint Hypermobility ◽  
Extracellular Matrix Protein ◽  
Adrenal Hyperplasia ◽  
Full Spectrum ◽  
Ehlers Danlos Syndrome ◽  
Cyp21a2 Gene ◽  
Salt Wasting

Mutations of the CYP21A2 gene encoding adrenal 21-hydroxylase cause congenital adrenal hyperplasia (CAH). The CYP21A2 gene is partially overlapped by the TNXB gene, which encodes an extracellular matrix protein called Tenascin-X (TNX). Mutations affecting both alleles of TNXB cause a severe, autosomal recessive form of Ehlers-Danlos syndrome (EDS). Rarely, patients with severe, salt-wasting CAH have deletions of CYP21A2 that extend into TNXB, resulting in a “contiguous gene syndrome” consisting of CAH and EDS. Heterozygosity for TNXB mutations causing haploinsufficiency of TNX may be associated with the mild “hypermobility form” of EDS, which principally affects small and large joints. Studies of patients with salt-wasting CAH found that up to 10% had clinical features of EDS, associated joint hypermobility, haploinsufficiency of TNX and heterozygosity for TNXB mutations, now called “CAH-X.” These patients have joint hypermobility and a spectrum of other comorbidities associated with their connective tissue disorder, including chronic arthralgia, joint subluxations, hernias, and cardiac defects. Other disorders are beginning to be associated with TNX deficiency, including familial vesicoureteral reflux and neurologic disorders. Further work is needed to delineate the full spectrum of TNX-deficient disorders, with and without associated CAH.

Ehlers-Danlos syndrome: molecular and clinical characterization of TNXA/TNXB chimeras in congenital adrenal hyperplasia

2021 ◽  
Author(s):  
Roxana Marino ◽  
Natalia Perez Garrido ◽  
Pablo Ramirez ◽  
Guillermo Notaristéfano ◽  
Angélica Moresco ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Gene Deletion ◽  
Joint Hypermobility ◽  
Sequencing Analysis ◽  
Adrenal Hyperplasia ◽  
Ehlers Danlos Syndrome ◽  
Cyp21a2 Gene ◽  
Number Of Patients ◽  
Contiguous Gene ◽  
Danlos Syndrome

Abstract Context The syndrome CAH-X is due to a contiguous gene deletion of CYP21A2 and TNXB resulting in TNXA/TNXB chimeras. Objective To analyze TNXB gene status and to clinically evaluate the Ehlers-Danlos syndrome phenotype in a large cohort of Argentine congenital adrenal hyperplasia (CAH) patients to assess the prevalence of this condition in our population. Design, settings, participants, intervention TNXB-gene analysis was performed in 66 non-related CAH patients that were carriers of the CYP21A2 gene deletion. A molecular strategy based on Multiplex ligation-dependent probe amplification and Sanger sequencing analysis was developed allowing for the detection of different, previously described TNXA/TNXB chimeras, named CH1, CH2, and CH3. Main outcome measures TNXB status of CAH patients that were carriers of the CYP21A2 deletion in the homozygous or heterozygous state. Results TNXA/TNXB CH1 was found in 41%, CH2 in 29% and CH3 in 1.5% of non-related alleles carrying the CYP21A2 deletion. Thus, overall 71% of alleles were found to carry a contiguous gene deletion. 67% of patients analyzed had a monoallelic and 6% a biallelic form. All patients with the biallelic form had severe skin hyperextensibility and generalized joint hypermobility. Conclusions Based on the high frequency of TNXB alterations in CYP21A2-deletion carrier alleles found, we recommend to evaluate TNXB status in these patients, and to assess connective tissue dysplasia including cardiologic alterations in positive cases. The number of patients undergoing cardiological evaluation should be expanded to determine the incidence of structural and functional abnormalities in this cohort.

Detection of a novel severe mutation affecting the CYP21A2 gene in a Chilean male with salt wasting congenital adrenal hyperplasia

Endocrine ◽  
2019 ◽  
Vol 67 (1) ◽  
pp. 258-263
Author(s):  
Eugenio Arteaga ◽  
Felipe Valenzuela ◽  
Carlos F. Lagos ◽  
Marcela Lagos ◽  
Alejandra Martinez ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene ◽  
Salt Wasting ◽  
Severe Mutation

scholarly journals Unusual Combination of MEN-1 and the Contiguous Gene Deletion Syndrome of CAH and Ehlers-Danlos Syndrome (CAH-X)

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Stanley M Chen Cardenas ◽  
Samer El-Kaissi ◽  
Ola Jarad ◽  
Muneezeh Liaqat ◽  
Márta Korbonits ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Gene Deletion ◽  
Deletion Syndrome ◽  
Adrenal Hyperplasia ◽  
Ehlers Danlos Syndrome ◽  
Cyp21a2 Gene ◽  
Men 1 ◽  
Contiguous Gene ◽  
Danlos Syndrome ◽  
Contiguous Gene Deletion Syndrome

Abstract The contiguous gene deletion syndrome of congenital adrenal hyperplasia and Ehlers-Danlos syndrome, named CAH-X, is a rare entity that occurs because of a deletion of a chromosomal area containing 2 neighboring genes, TNXB and CYP21A. Here, we describe a patient from a consanguineous family in which coincidentally MEN-1 syndrome is associated with CAH-X, causing particular challenges explaining the phenotypic features of the patient. A 33-year-old man with salt-wasting congenital adrenal hyperplasia and classic-like Ehlers-Danlos syndrome presented with an adrenal crisis with a history of recurrent hypoglycemia, abdominal pain, and vomiting. He was found to have primary hyperparathyroidism, hyperprolactinemia, and pancreatic neuroendocrine tumors, as well as primary hypogonadism, large adrenal myelolipomas, and low bone mineral density. A bladder diverticulum was incidentally found. Genetic analysis revealed a heterozygous previously well-described MEN1 mutation (c.784-9G > A), a homozygous complete deletion of CYP21A2 (c.1-?_1488+? del), as well as a large deletion of the neighboring TNXB gene (c.11381-?_11524+?). The deletion includes the complete CYP21A2 gene and exons 35 through 44 of the TNXB gene. CGH array found 12% homozygosity over the whole genome. This rare case illustrates a complex clinical scenario with some initial diagnostic challenges.

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis

2019 ◽  
Vol 51 (09) ◽  
pp. 586-594 ◽  
Author(s):  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
Meropi Toumba ◽  
Charilaos Stylianou ◽  
Michalis Picolos ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Salt Wasting ◽  
Greek Cypriot ◽  
Frequent Mutations ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency ◽  
Greek Cypriots

AbstractCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is caused by mutations in the CYP21A2 gene. The study refers to CAH patients of Greek-Cypriot ancestry between years 2007 and 2018. One hundred and twenty patients with various degrees of CAH were categorized and genotyped. The patients were categorized in 4 mutation groups based on their clinical and biochemical findings. The majority of patients (85.0%) belonged to the non-classic (NC)-CAH form and the disorder was more often diagnosed in females (71.7%). The most severe classic salt-wasting (SW) form was identified in 11 neonates (9.2%). Seven (5.8%) children were also identified with the simple virilizing (SV) form and a median presentation age of 5 years [interquartile range (IQR) 3.2–6.5]. In the 240 nonrelated alleles, the most frequent mutation was p.Val281Leu (60.0%) followed by c.655 A/C>G (IVS2–13A/C>G) (8.8%), p.Pro453Ser (5.8%), DelEx1–3 (4.6%), p.Val304Met (4.6%), and p.Gln318stop (4.2%). Other less frequent mutations including rare deletions were also identified. Following our recent report that the true carrier frequency of CYP21A2 in Greek-Cypriots is 1:10, this study reports that the CAH prevalence is predicted around 1.7 cases per 10 000 people. Therefore, the up-to-date 120 CAH patients identified by our group make only the 6.9% of the ones estimated (approximately 1750) to exist in the Greek Cypriot population. The compiled data from a coherent population such as the Greek-Cypriot could be valuable for the antenatal diagnosis, management and genetic counselling of the existing and prospect families with CAH.

scholarly journals Concurrence of Meningomyelocele and Salt-Wasting Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Heves Kırmızıbekmez ◽  
Rahime Gül Yesiltepe Mutlu ◽  
Serdar Moralıoğlu ◽  
Ahmet Tellioğlu ◽  
Ayşenur Cerrah Celayir
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Growth Retardation ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Significant Regression ◽  
One Year ◽  
The One ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited defects of cortisol biosynthesis. A case of classical CAH due to 21-hydroxylase deficiency (21-OHD) with early onset of salt waste and concurrence of meningomyelocele (MMC) was presented here. The management of salt-wasting crisis which is complicated by a postrenal dysfunction due to neurogenic bladder was described. Possible reasons of growth retardation in the one-year follow-up period were discussed. A significant regression of the phallus with proper medical treatment was also mentioned.

Aldosterone Synthesis in Salt-Wasting Congenital Adrenal Hyperplasia with Complete Absence of Adrenal 21-Hydroxylase

1991 ◽  
Vol 324 (3) ◽  
pp. 145-149 ◽  
Author(s):  
Phyllis W. Speiser ◽  
Levon Agdere ◽  
Hajime Ueshiba ◽  
Perrin C. White ◽  
Maria I. New
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Salt Wasting
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