scholarly journals Variations in the 3′UTR of theCYP21A2Gene in Heterozygous Females with Hyperandrogenaemia

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
Meropi Toumba ◽  
Alexia A. P. Phedonos ◽  
Michalis Picolos ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Untranslated Regions ◽  
Heterozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Mild Form ◽  
Increased Risk ◽  
Female Children ◽  
17 Hydroxyprogesterone ◽  
Genotype Correlation

Heterozygosity forCYP21A2mutations in females is possibly related to increased risk of developing clinical hyperandrogenism. The present study was designed to seek evidence on the phenotype-genotype correlation in female children, adolescents, and women withCYP21A2mutations and variants in the 3′UTR region of the gene. Sixty-six patients out of the 169 were identified as carriers ofCYP21A2mutations. Higher values of stimulated 17 hydroxyprogesterone (17-OHP) levels were found in the carriers of the p.Val281Leu mutation compared to the carriers of other mutations (mean: 24.7 nmol/l versus 15.6 nmol/l). The haplotype of the∗52C>T,∗440C>T, and∗443T>C in the 3′UTR was identical in all heterozygous patients with p.Val281Leu and the haplotype of the∗12C>T and∗52C>T was identical in all heterozygous patients with the p.Gln318∗. In conclusion, hyperandrogenaemic females are likely to bear heterozygousCYP21A2mutations. Carriers of the mild p.Val281Leu mutation are at higher risk of developing hyperandrogenism than the carriers of more severe mutations. The identification of variants in the 3′UTR ofCYP21A2in combination with the heterozygous mutation may be associated with the mild form of nonclassic congenital adrenal hyperplasia and reveal the importance of analyzing theCYP21A2untranslated regions for the appropriate management of this category of patients.

Serum 3α-androstanediol glucuronide measurements in children with congenital adrenal hyperplasia

1994 ◽  
Vol 131 (5) ◽  
pp. 504-508 ◽  
Author(s):  
Sükrü Hatun ◽  
Nurşen Yordam ◽  
Ali Süha Çalikoǧlu
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Control Group ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Female Children ◽  
The Mean ◽  
Simple Virilizing ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Androstanediol Glucuronide

Hatun Ş, Yordam N, Çalikoǧlu AS. Serum 3α-androstandiol glucuronide measurements in children with congenital adrenal hyperplasia. Eur J Endocrinol 1994;131:504–8. ISSN 0804–4643 To determine the value of 3α-androstanediol glucuronide (3-AG) measurements in children with congenital adrenal hyperplasia, we compared serum 3AG, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) levels and 24-h urinary 17-ketosteroid (17-KS) excretion in 42 female children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, including 27 with the simple virilizing and 15 with the salt-losing form. Their mean age was 74.5 ±48.5 months (range, 6–194 months). Twenty-four-hour urinary 17-KS excretion and serum 3-AG, A, T, DHT and 17-OHP levels were measured in the patients. The values were less than the mean + 2 sd of the control group in 63%, 74%, 67%, 69%, 60% and 31% of the patients, respectively. Serum 3-AG levels correlated with 24-h urinary 17-KS excretion (r = 0.66) and plasma A (r = 0.80), 17-OHP (r = 0.56), T (r = 0.79) and DHT (r = 0.62) levels. We conclude that serum 3-AG is a useful metabolic index in the management of children with congenital adrenal hyperplasia. Şükrü Hatun, Türk-İş Blk, 274/7, Aydinlikevler, Ankara, Turkey

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.

Screening for Congenital Adrenal Hyperplasia: The Delfia Screening Test Overestimates Serum 17-Hydroxyprogesterone in Preterm Infants

PEDIATRICS ◽  
1996 ◽  
Vol 97 (1) ◽  
pp. 100-102 ◽  
Author(s):  
Saad Al Saedi ◽  
Heather Dean ◽  
William Dent ◽  
Elizabeth Stockl ◽  
Catherine Cronin
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Preterm Infants ◽  
Gestational Age ◽  
Adrenal Hyperplasia ◽  
Blood Spots ◽  
Healthy Infants ◽  
Extraction Step ◽  
Postconceptional Age ◽  
17 Hydroxyprogesterone ◽  
Over Time

Objective. To compare 17-hydroxyprogesterone (17-OHP) levels measured by quantitative serum radioimmunoassay (RIA), including an extraction step, and by screening fluoroimmnoassay (FIA) on blood spots in preterm infants. Methods. Subjects were 39 healthy infants born at less than 31 weeks' gestational age. Each infant had weekly blood sampling, and RIA and FIA were performed on each sample. Results. Two hundred twenty-seven samples were taken at 28 to 41 weeks' postconceptional age. Mean ± SD 17-OHP measured by RIA was 11.4 ± 11.1 nmol/L (0.4 ± 0.4 µg/dL), and decreased over time. Mean ± SD 17-OHP measured by FIA was 38.96 ± 37.3 nmol/L, greater than 17-OHP (RIA). Log(δFIA-RIA) was inversely related to postconceptional age (R2 = .39). Conclusion. Screening FIA of blood spots overestimates levels of 17-OHP in preterm infants and should not be used to determine the likelthood of congenital adrenal hyperplasia in this population. We have abandoned FIA screening for congenital adrenal hyperplasia in infants weiging less than 1500 g.

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