Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency in the Mexican population: identification of possible new mutations and high prevalence of apparent germ-line mutations

1998 ◽  
Vol 102 (2) ◽  
pp. 170-177 ◽  
Author(s):  
Maria Luisa Ordoñez-Sánchez ◽  
Salvador Ramírez-Jiménez ◽  
Antonio Ulises López-Gutierrez ◽  
Laura Riba ◽  
Salvador Gamboa-Cardiel ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Germ Line ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Mexican Population ◽  
Hydroxylase Deficiency ◽  
High Prevalence ◽  
Germ Line Mutations ◽  
21 Hydroxylase Deficiency ◽  
New Mutations

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene

2020 ◽  
Author(s):  
Berta Carvalho ◽  
C.Joana Marques ◽  
Rita Santos-Silva ◽  
Manuel Fontoura ◽  
Davide Carvalho ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Late Onset ◽  
Molecular Genetic Analysis ◽  
Clinical Severity ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Pathogenic Variants ◽  
21 Hydroxylase Deficiency

AbstractCongenital Adrenal Hyperplasia is a group of genetic autosomal recessive disorders that affects adrenal steroidogenesis in the adrenal cortex. One of the most common defects associated with Congenital Adrenal Hyperplasia is the deficiency of 21-hydroxylase enzyme, responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. The impairment of cortisol and aldosterone production is directly related to the clinical form of the disease that ranges from classic or severe to non-classic or mild late onset. The deficiency of 21-hydroxylase enzyme results from pathogenic variants on CYP21A2 gene that, in the majority of the cases, compromise enzymatic activity and are strongly correlated with the clinical severity of the disease. Due to the exceptionally high homology and proximity between the gene and the pseudogene, more than 90% of pathogenic variants result from intergenic recombination. Around 75% are deleterious variants transferred from the pseudogene by gene conversion, during mitosis. About 20% are due to unequal crossing over during meiosis and lead to duplications or deletions on CYP21A2 gene. Molecular genetic analysis of CYP21A2 variants is of major importance for confirmation of clinical diagnosis, predicting prognosis and for an appropriate genetic counselling. In this review we will present an update on the genetic analysis of CYP21A2 gene variants in CAH patients performed in our department.

scholarly journals Rapid Second-Tier Molecular Genetic Analysis for Congenital Adrenal Hyperplasia Attributable to Steroid 21-Hydroxylase Deficiency

2005 ◽  
Vol 51 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Siegfried Kösel ◽  
Siegfried Burggraf ◽  
Ralph Fingerhut ◽  
Helmut G Dörr ◽  
Adelbert A Roscher ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
False Positives ◽  
High Rate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21 Gene ◽  
Second Tier ◽  
21 Hydroxylase Deficiency

Abstract Background: Neonatal screening for steroid 21-hydroxylase (CYP21) deficiency is performed to identify congenital adrenal hyperplasia (CAH). The immunologic assay for 17α-hydroxyprogesterone (17-OHP) has a high rate of false positives. We assessed the potential for increasing the specificity for CAH by use of a second step involving analysis of the CYP21 gene. Methods: Between January 1999 and December 2003, a total of 810 000 newborns were screened. Of these, 7920 had to be retested because their 17-OHP values were above the cutoff of the assay. Sixty-one had positive 17-OHP values in their recall samples and were diagnosed as having CAH. We used a rapid assay for common mutations of the CYP21 gene to analyze these 61 samples. In a prospective study, 198 consecutive samples that had increased 17-OHP and 100 samples that had normal 17-OHP concentrations were genotyped. Results: Fifty-nine of 61 cases diagnosed as having CAH were confirmed genetically as CYP21 deficiencies. One patient had a 3β-hydroxysteroid dehydrogenase deficiency, and one patient carried no CYP21 mutations. The 198 increased 17-OHP results were designated as false positives after immunologic testing of recall samples. None of these samples exhibited the genetic pattern consistent with CYP21 deficiency. Conclusions: If samples with increased 17-OHP values were screened genetically, the number of retests would decrease by ∼90%, but the overall sensitivity of CAH screening would remain the same. Adding a second-tier genetic step would require a modest increase in costs, but is counterbalanced by fewer recalls, less clinical follow-up, and a reduction in unnecessary worry for families.

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