scholarly journals Frequency of CYP21 Gene Mutations in Czech Patients with Steroid 21-Hydroxylase Deficiency and Statistical Comparison with Other Populations

2003 ◽  
Vol 12 (4) ◽  
pp. 243-247 ◽  
Author(s):  
Karel Kotaška ◽  
Richard Průša
Keyword(s):  
Gene Mutations ◽  
Hydroxylase Deficiency ◽  
Statistical Comparison ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

Screening of CYP21 gene mutations in 129 French patients affected by steroid 21-hydroxylase deficiency

1995 ◽  
Vol 5 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Benoit Barbat ◽  
Any Bogyo ◽  
Marie-Charles Raux-Demay ◽  
Frédéarique Kuttenn ◽  
Joelle Boué ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Hydroxylase Deficiency ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

scholarly journals Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

1999 ◽  
pp. 132-139 ◽  
Author(s):  
V Dolzan ◽  
J Prezelj ◽  
B Vidan-Jeras ◽  
K Breskvar
Keyword(s):  
Molecular Analysis ◽  
Gene Mutations ◽  
Hla Typing ◽  
Carrier Status ◽  
Acth Stimulation ◽  
Adrenal Androgen ◽  
Hydroxylase Deficiency ◽  
Predictive Values ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

OBJECTIVE: To study the incidence of 21-hydroxylase deficiency in Slovenian hyperandrogenic women, at the gene level. Previous endocrine studies indicated large differences in the incidence of 21-hydroxylase deficiency in hyperandrogenic women. The predictive values of the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation and of HLA typing in screening for carrier status were re-evaluated. DESIGN: Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women. MEASUREMENTS: Cortisol and 17-OHP concentrations were measured at baseline and 60 min after ACTH stimulation. Basal adrenal androgen concentrations were also measured. RESULTS: None of 83 hyperandrogenic patients was affected with non-classical 21-hydroxylase deficiency, but 12 of 81 patients (14.8%) had high concentrations of 17-OHP after stimulation, indicative of carrier status. The increase in 17-OHP concentrations could be explained by a carrier status for CYP21 gene mutations in only three of 12 patients (25%), whereas seven of 69 patients (10. 1%) with normal concentrations of 17-OHP after stimulation were found to be carriers of CYP21 gene mutations, indicating low positive predictive values of ACTH stimulation as a screening test for carriers of 21-hydroxylase deficiency. In total, 11 carriers were identified among 83 patients: seven CYP21 gene deletions/conversions, two Gln(318)Stop and one Val(281)Leu mutation and one gene conversion extending from exon 4 to exon 7 were found. The association between Val(281)Leu mutation and HLA-B14 antigen was confirmed in this Slovenian population. CONCLUSIONS: Basal or ACTH-stimulated 17-OHP concentrations are not a good indicator of the carrier status for 21-hydroxylase deficiency among Slovenian hyperandrogenic patients. Reliable screening for carriers of 21-hydroxylase deficiency is possible only by molecular analysis of the CYP21 gene.

scholarly journals Variable ACTH-Stimulated 17-Hydroxyprogesterone Values in 21-Hydroxylase Deficiency Carriers Are Not Related to the Different CYP21 Gene Mutations

2002 ◽  
Vol 87 (2) ◽  
pp. 786-790 ◽  
Author(s):  
Tânia A. S. S. Bachega ◽  
Enecy M. L. Brenlha ◽  
Ana E. C. Billerbeck ◽  
José A. M. Marcondes ◽  
Guiomar Madureira ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Hydroxylase Deficiency ◽  
Cyp21 Gene ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

scholarly journals CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

2008 ◽  
Vol 31 (3) ◽  
pp. 626-631 ◽  
Author(s):  
Tarcísio André Amorim de Carvalho ◽  
Izabel Cristina Neves de Souza ◽  
France Keiko Nascimento Yoshioka ◽  
Milena Coelho Fernandes Caldato ◽  
Nilza Nei Torres ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Amazon Region ◽  
Hydroxylase Deficiency ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

scholarly journals Characterisation of three novel CYP11B1 mutations in classic and non-classic 11β-hydroxylase deficiency

2014 ◽  
Vol 170 (5) ◽  
pp. 697-706 ◽  
Author(s):  
Seher Polat ◽  
Alexandra Kulle ◽  
Züleyha Karaca ◽  
Ilker Akkurt ◽  
Selim Kurtoglu ◽  
...  
Keyword(s):  
Expression System ◽  
Three Dimensional ◽  
Gene Mutations ◽  
Dimensional Structure ◽  
Hydroxylase Deficiency ◽  
Mutant Proteins ◽  
Maximum Reaction ◽  
Functional Consequences ◽  
21 Hydroxylase Deficiency

BackgroundCongenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine diseases. Steroid 11β-hydroxylase (P450c11) deficiency (11OHD) is the second most common form of CAH.AimThe aim of the study was to study the functional consequences of three novelCYP11B1gene mutations (p.His125Thrfs*8, p.Leu463_Leu464dup and p.Ser150Leu) detected in patients suffering from 11OHD and to correlate this data with the clinical phenotype.MethodsFunctional analyses were done by using a HEK293 cellin vitroexpression system comparing WT with mutant P450c11 activity. Mutant proteins were examinedin silicoto study their effect on the three-dimensional structure of the protein.ResultsTwo mutations (p.His125Thrfs*8 and p.Leu463_Leu464dup) detected in patients with classic 11OHD showed a complete loss of P450c11 activity. The mutation (p.Ser150Leu) detected in a patient with non-classic 11OHD showed partial functional impairment with 19% of WT activity.ConclusionFunctional mutation analysis enables the correlation of novelCYP11B1mutations to the classic and non-classic 11OHD phenotype respectively. Mutations causing a non-classic phenotype show typically partial impairment due to reduced maximum reaction velocity comparable with non-classic mutations in 21-hydroxylase deficiency. The increasing number of mutations associated with non-classic 11OHD illustrate that this disease should be considered as diagnosis in patients with otherwise unexplained hyperandrogenism.

scholarly journals Potential advantage of N363S glucocorticoid receptor polymorphism in 21-hydroxylase deficiency

2006 ◽  
Vol 154 (6) ◽  
pp. 859-864 ◽  
Author(s):  
A Luczay ◽  
D Török ◽  
A Ferenczi ◽  
J Majnik ◽  
J Sólyom ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Plasma Renin ◽  
Hydroxylase Deficiency ◽  
Laboratory Findings ◽  
Specific Pcr ◽  
Cyp21 Gene ◽  
Significant Difference ◽  
Allele Specific ◽  
21 Hydroxylase Deficiency

Objective: Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients. Design: CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively. Methods: The CYP21 gene of 200 CAH patients was analyzed by allele-specific PCR. The GR gene was tested for N363S by PCR followed by restriction fragment length polymorphism. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, dehydroepiandrosterone (DHEA), aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed. Results: The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference between the carriers and non-carriers in either the substitution doses, the hormonal, or the auxiological parameters. Conclusions: The association of sensitizing the GR variant with impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimes.

scholarly journals Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche

2011 ◽  
Vol 165 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Lucia Ghizzoni ◽  
Marco Cappa ◽  
Alessandra Vottero ◽  
Graziamaria Ubertini ◽  
Daniela Carta ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Serum Levels ◽  
Cortisol Response ◽  
Operating Characteristics ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
17 Hydroxyprogesterone ◽  
Italian Children ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

ObjectivePremature pubarche (PP) is the most frequent sign of nonclassic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency in childhood. The aim of this study was to assess the relationship between the CYP21A2 genotype and baseline and ACTH-stimulated 17-hydroxyprogesterone (17-OHP) and cortisol serum levels in patients presenting with PP.Patients and methodsA total of 152 Italian children with PP were studied. Baseline and ACTH-stimulated 17-OHP and cortisol serum levels were measured and CYP21A2 gene was genotyped in all subjects.ResultsBaseline and ACTH-stimulated serum 17-OHP levels were significantly higher in NCCAH patients than in both heterozygotes and children with idiopathic PP (IPP). Of the patient population, four NCCAH patients (7.3%) exhibited baseline 17-OHP values <2 ng/ml (6 nmol/l). An ACTH-stimulated 17-OHP cutoff level of 14 ng/ml (42 nmol/l) identified by the receiver-operating characteristics curves showed the best sensitivity (90.9%) and specificity (100%) in distinguishing NCCAH patients. This value, while correctly identifying all unaffected children, missed 9% of affected individuals. Cortisol response to ACTH stimulation was <18.2 μg/dl (500 nmol/l) in 14 NCCAH patients (28%) and none of the heterozygotes or IPP children. Among the 55 NCCAH patients, 54.5% were homozygous for mild CYP21A2 mutations, 41.8% were compound heterozygotes for one mild and one severe CYP21A2 gene mutations, and 3.6% had two severe CYP21A2 gene mutations.ConclusionIn children with PP, baseline 17-OHP levels are not useful to rule out the diagnosis of NCCAH, which is accomplished by means of ACTH testing only. The different percentages of severe and mild CYP21A2 gene mutations found in PP children compared with adult NCCAH patients is an indirect evidence that the enzyme defect is under-diagnosed in childhood, and it might not lead to the development of hyperandrogenic symptoms in adulthood. Stress-dose glucocorticoids should be considered in patients with suboptimal cortisol response to ACTH stimulation.

scholarly journals Three Novel Mutations in CYP21 Gene in Brazilian Patients with the Classical Form of 21-Hydroxylase Deficiency Due to a Founder Effect

2002 ◽  
Vol 87 (9) ◽  
pp. 4314-4317 ◽  
Author(s):  
Ana Elisa C. Billerbeck ◽  
Berenice B. Mendonca ◽  
Emilia M. Pinto ◽  
Guiomar Madureira ◽  
Ivo J. P. Arnhold ◽  
...  
Keyword(s):  
Founder Effect ◽  
Novel Mutations ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

scholarly journals Molecular Analysis of CYP21A2 Gene Mutations among Iraqi Patients with Congenital Adrenal Hyperplasia

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ruqayah G. Y. Al-Obaidi ◽  
Bassam M. S. Al-Musawi ◽  
Munib Ahmed K. Al-Zubaidi ◽  
Christian Oberkanins ◽  
Stefan Németh ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Analysis ◽  
Point Mutations ◽  
Gene Mutations ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Gene Deletions ◽  
Large Gene ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia is a group of autosomal recessive disorders. The most frequent one is 21-hydroxylase deficiency. Analyzing CYP21A2 gene mutations was so far not reported in Iraq. This work aims to analyze the spectrum and frequency of CYP21A2 mutations among Iraqi CAH patients. Sixty-two children were recruited from the Pediatric Endocrine Consultation Clinic, Children Welfare Teaching Hospital, Baghdad, Iraq, from September 2014 till June 2015. Their ages ranged between one day and 15 years. They presented with salt wasting, simple virilization, or pseudoprecocious puberty. Cytogenetic study was performed for cases with ambiguous genitalia. Molecular analysis of CYP21A2 gene was done using the CAH StripAssay (ViennaLab Diagnostics) for detection of 11 point mutations and >50% of large gene deletions/conversions. Mutations were found in 42 (67.7%) patients; 31 (50%) patients were homozygotes, 9 (14.5%) were heterozygotes, and 2 (3.2%) were compound heterozygotes with 3 mutations, while 20 (32.3%) patients had none of the tested mutations. The most frequently detected mutations were large gene deletions/conversions found in 12 (19.4%) patients, followed by I2Splice and Q318X in 8 (12.9%) patients each, I172N in 5 (8.1%) patients, and V281L in 4 (6.5%) patients. Del 8 bp, P453S, and R483P were each found in one (1.6%) and complex alleles were found in 2 (3.2%). Four point mutations (P30L, Cluster E6, L307 frameshift, and R356W) were not identified in any patient. In conclusion, gene deletions/conversions and 7 point mutations were recorded in varying proportions, the former being the commonest, generally similar to what was reported in regional countries.

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