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.

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.

scholarly journals Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Vipula Kolli ◽  
Hannah Kim ◽  
Hamsini Rao ◽  
Qizong Lao ◽  
Alison Gaynor ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Gene Deletion ◽  
Deletion Syndrome ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Ehlers Danlos Syndrome ◽  
Amino Terminal ◽  
Contiguous Gene ◽  
21 Hydroxylase Deficiency ◽  
Contiguous Gene Deletion Syndrome

Abstract Objective Approximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disrupts CYP21A2 and the flanking TNXB gene resulting in CAH-X, a contiguous gene deletion syndrome. TNXB encodes tenascin-X (TNX), an extracellular matrix glycoprotein that plays an important role in collagen organization. TNXB impairment is associated with Ehlers–Danlos syndrome. Symptoms include joint hypermobility, hernias and cardiac defects. We measured serum TNX using an antibody targeting the amino-terminal of the TNX protein in 161 subjects, including extensively genotyped and phenotyped CAH patients, their relatives, and healthy controls. Results We evaluated the potential of serum TNX as a screening tool for CAH-X. CAH-X patients, especially haploinsufficient patients carrying the TNXA-TNXB chimeric gene CAH-X-CH-1 showed reduced TNX levels compared to controls (P < 0.05). TNX levels were similar in all subjects carrying a TNXB mutation. However, CAH patients who did not harbor a TNXB mutation also had reduced TNX compared to controls (P < 0.001). Thus, measuring serum TNX is not an effective screen for CAH-X amongst patients with CAH. TNXB genotyping is recommended for CAH patients who have symptoms of a connective tissue disorder. Epigenetic factors that influence TNX expression require further study.

scholarly journals Haploinsufficiency ofALX4as a Potential Cause of Parietal Foramina in the 11p11.2 Contiguous Gene–Deletion Syndrome

2000 ◽  
Vol 67 (5) ◽  
pp. 1327-1332 ◽  
Author(s):  
Yuan‐Qing Wu ◽  
Jose L. Badano ◽  
Christopher McCaskill ◽  
Hannes Vogel ◽  
Lorraine Potocki ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Deletion Syndrome ◽  
Contiguous Gene ◽  
Contiguous Gene Deletion Syndrome

Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion

2014 ◽  
Vol 8 (4) ◽  
pp. 139-145 ◽  
Author(s):  
Mariana Moysés-Oliveira ◽  
Tatiane I. Mancini ◽  
Sylvia S. Takeno ◽  
Andressa D.S. Rodrigues ◽  
Tania A.S.S. Bachega ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Ovarian Failure ◽  
Adrenal Hyperplasia ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

scholarly journals Chromosome 16p13.3 Contiguous Gene Deletion Syndrome including the SLX4, DNASE1, TRAP1, and CREBBP Genes Presenting as a Relatively Mild Rubinstein–Taybi Syndrome Phenotype: A Case Report of a Saudi Boy

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Mohammad M. Al-Qattan ◽  
Zuhair A. Rahbeeni ◽  
Zuhair N. Al-Hassnan ◽  
Abdulaziz Jarman ◽  
Atif Rafique ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Deletion Syndrome ◽  
Syndrome Type ◽  
Partial Deletion ◽  
Gene Deletions ◽  
Mild Phenotype ◽  
Contiguous Gene ◽  
Chromosome 16P13.3 ◽  
Contiguous Gene Deletion Syndrome

The classic Rubinstein–Taybi syndrome Type 1 (RSTS1, OMIM 180849) is caused by heterozygous mutations or deletions of the CREBBP gene. Herein, we describe the case of a Saudi boy with chromosome 16p13.3 contiguous gene deletion syndrome (OMIM 610543) including the SLX4, DNASE1, TRAP1, and CREBBP genes, but presenting with a relatively mild RSTS1 syndrome phenotype. Compared with previously reported cases with severe phenotypes associated with 16p13.3 contiguous gene deletions, our patient had partial deletion of the CREBBP gene (with a preserved 5′ region), which might explain his relatively mild phenotype.

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