A Novel Nonsense Mutation c.374C>G in CYP21A2 Gene of a Vietnamese Patient with Congenital Adrenal Hyperplasia

2018 ◽  
pp. 27-35
Author(s):  
Chi Dung Vu ◽  
Thanh Van Ta ◽  
Ngoc-Lan Nguyen ◽  
Huy-Hoang Nguyen ◽  
Thi Kim Lien Nguyen ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Nonsense Mutation ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene

scholarly journals ID: 1048 A novel nonsense mutation in the CYP21A2 gene of a Vietnamese patient with congenital adrenal hyperplasia

2017 ◽  
Vol 4 (S) ◽  
pp. 129
Author(s):  
Vu Chi Dung ◽  
Ngoc Lan Nguyen ◽  
Huy Hoang Nguyen ◽  
Thi Kim Lien Nguyen ◽  
Thinh Huy Tran ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Nonsense Mutation ◽  
Stop Codon ◽  
Large Deletion ◽  
Heterozygous Mutation ◽  
Normal Allele ◽  
Adrenal Hyperplasia ◽  
Steroid Synthesis ◽  
Cyp21a2 Gene ◽  
Exon 1

Inactivating mutations in the CYP21A2 gene which encodes the protein involved in steroid synthesis have been reported in the patients with congenital adrenal hyperplasia (CAH). An infant who diagnosed with the severe phenotype of CAH such as increasing testicular volume, elevating of 17-hydroxyprogesteron, testosterone and progesterone and his family were subjected for genetic studies. Initially, we used PCR and direct sequencing to screen mutations in the CYP21 gene in the proband and his family. We identified a novel nonsense mutation c.374C>G predicts a substitution of serine for a stop codon at codon 125 (p.S125*) within exon 3 in the proband. However, the inheritance pattern of the mutation was not consistent with disease causation because of a heterozygous mutation carrier in father and sibling, wild-type alleles in mother but mutant alleles in proband. This inspired us to find deletions of exon using multiplex ligation-dependent probe amplification (MLPA) assay. In the profiles of MLPA electropherogram, the proband had a large deletion in exon 3, but his mother did not have. It means that the proband inherited a normal allele from his mother and a mutant allele from his father, but the deletion of a normal allele occurred in the proband. Therefore, mutation c.374C>G (p.S125*) in exon 3 in the proband is considered as a heterozygous deletion mutation. In addition, a large deletion in exon 1 in the maternal allele in the proband is observed. Taking together, the proband carried a nonsense mutation accompanied with two deletions in exon 1 and exon 3 in the CYP21A2 gene affect the CAH phenotype severity. These mutations also expand the CYP21A2 mutation spectrum in CAH disorder. This case also highlights the need of caution when interpreting results of molecular genetics and biochemical testing during genetic counseling.

Molecular Analysis of CYP21A2 Gene Mutations among Congenital Adrenal Hyperplasia Patients in Iraq

2021 ◽  
pp. 82-92
Author(s):  
Ruqayah G. Y. Al-Obaidi ◽  
Bassam M. S. Al-Musawi ◽  
Munib Ahmed K. AlZubaidi ◽  
Christian Oberkanins ◽  
Stefan Németh ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Analysis ◽  
Gene Mutations ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene

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.

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 Molecular genetic strategy for diagnosis of congenital adrenal hyperplasia in Serbia

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 457-467 ◽  
Author(s):  
Milena Ugrin ◽  
Iva Milacic ◽  
Anita Skakic ◽  
Kristel Klaassen ◽  
Jovana Komazec ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Congenital Adrenal Hyperplasia ◽  
Direct Sequencing ◽  
Molecular Genetic ◽  
Gene Rearrangements ◽  
Molecular Genetic Testing ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene ◽  
Classical Form ◽  
Large Gene

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common endocrine diseases, yet genetic diagnosis is among the most complicated of all monogenic disorders. It has an overall incidence of 1:10000-1:20000, it is inherited in autosomal recessive pattern and caused by mutations affecting CYP21A2 gene. Based on the phenotypic expression, this disease is categorized into severe, classical form revealed at birth and mild, non-classical form. Although diagnosis could be established based on biochemical tests and distinctive clinical features, molecular genetic testing is crucial for diagnosis confirmation, detection of carriers and asymptomatic patients, disease prognosis, as well as for providing proper genetic counselling and prenatal diagnosis. Based on CYP21A2 mutational spectrum and frequencies in Serbia, in this paper we propose an optimal molecular genetic diagnostic algorithm for CAH and discuss genetic mechanisms underlying the disease. The complete diagnostic procedure combines multiplex minisequencing technique (SNaPshot PCR) as a method for rapid detection of common point mutations, direct sequencing of whole CYP21A2 gene and PCR with sequence specific primers (PCR-SSP) for large gene rearrangements detection (CYP21A1P/CYP21A2 chimeras). While SNaPshot PCR assay analyses ten common mutations (c.290-13A/C>G, p.P30L, p.R356W, p.G110fs, p.V281L, p.Q318X, p.L307fs, p.I172N, Cluster p.[I236N;V237E;M239K] and p.P453S) which account for over 80% of all CYP21A2 mutations in Serbian population, direct sequencing of CYP21A2 gene is needed to identify potential rare or novel mutations present in Serbian population with frequency of 1.8%. Additionally, large gene rearrangements which are present with frequency of 16.7% make PCR-SSP analysis an unavoidable part of molecular characterization of CAH in Serbia. Described molecular genetic strategy is intended to facilitate correct diagnosis assessment in CAH affected individuals and their families in Serbia but it will also contribute to molecular genetic testing of CAH patients across Europe.

scholarly journals Investigation of Copy Number Changes in CYP21A2 Gene By Using MLPA Technique in Patients with Congenital Adrenal Hyperplasia

2020 ◽  
Vol 2 (1) ◽  
pp. 1-10
Author(s):  
Bakhtiyar MAMMADOV ◽  
Aysel KALAYCI YİĞİN ◽  
Filiz ÖZDEMİR ◽  
Ahmet ÖZAYDIN ◽  
Mehmet SEVEN
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Copy Number ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene ◽  
Copy Number Changes
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