Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach
Adrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific P...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.834549/full |
| _version_ | 1819174977407025152 |
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| author | María Arriba María Arriba Begoña Ezquieta Begoña Ezquieta |
| author_facet | María Arriba María Arriba Begoña Ezquieta Begoña Ezquieta |
| author_sort | María Arriba |
| collection | DOAJ |
| description | Adrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific PCR, accurate definition of pseudogene-gene chimeras, gene duplications and allele dropout avoidance. A small panel of well-established disease-causing alterations enables a high diagnostic yield in confirming/discarding the disorder not only in symptomatic patients but also in those asymptomatic with borderline/positive results of 17-hydroxyprogesterone. Unfortunately, the complexity of this locus makes it today reluctant to high throughput techniques of massive sequencing. The strong relationship existing between the molecular alterations and the degree of enzymatic deficiency has allowed genetic studies to demonstrate its usefulness in predicting/classifying the clinical form of the disease. Other aspects of interest regarding molecular studies include its independence of physiological variations and analytical interferences, its usefulness in the diagnosis of simple virilizing forms in males and its inherent contribution to the genetic counseling, an aspect of great importance taking into account the high carrier frequency of CAH in the general population. Genetic testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples. It is also helpful in areas such as assisted reproduction and preimplantation diagnosis. Molecular diagnosis of 21-OHD under expert knowledge definitely contributes to a better management of the disease in every step of the clinical course. |
| first_indexed | 2024-12-22T20:47:32Z |
| format | Article |
| id | doaj.art-cc9a8499abc3419a8d951004805073dc |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-22T20:47:32Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-cc9a8499abc3419a8d951004805073dc2022-12-21T18:13:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-03-011310.3389/fendo.2022.834549834549Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical ApproachMaría Arriba0María Arriba1Begoña Ezquieta2Begoña Ezquieta3Molecular Diagnostics Laboratory, Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), Madrid, SpainMolecular Diagnostics Laboratory, Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), Madrid, SpainAdrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific PCR, accurate definition of pseudogene-gene chimeras, gene duplications and allele dropout avoidance. A small panel of well-established disease-causing alterations enables a high diagnostic yield in confirming/discarding the disorder not only in symptomatic patients but also in those asymptomatic with borderline/positive results of 17-hydroxyprogesterone. Unfortunately, the complexity of this locus makes it today reluctant to high throughput techniques of massive sequencing. The strong relationship existing between the molecular alterations and the degree of enzymatic deficiency has allowed genetic studies to demonstrate its usefulness in predicting/classifying the clinical form of the disease. Other aspects of interest regarding molecular studies include its independence of physiological variations and analytical interferences, its usefulness in the diagnosis of simple virilizing forms in males and its inherent contribution to the genetic counseling, an aspect of great importance taking into account the high carrier frequency of CAH in the general population. Genetic testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples. It is also helpful in areas such as assisted reproduction and preimplantation diagnosis. Molecular diagnosis of 21-OHD under expert knowledge definitely contributes to a better management of the disease in every step of the clinical course.https://www.frontiersin.org/articles/10.3389/fendo.2022.834549/fullccongenital adrenal hyperplasia (CAH)21-hydroxylase deficiencyCYP21A2 geneclassical forms of congenital adrenal hyperplasianon-classical forms of congenital adrenal hyperplasiamolecular diagnosis |
| spellingShingle | María Arriba María Arriba Begoña Ezquieta Begoña Ezquieta Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach Frontiers in Endocrinology ccongenital adrenal hyperplasia (CAH) 21-hydroxylase deficiency CYP21A2 gene classical forms of congenital adrenal hyperplasia non-classical forms of congenital adrenal hyperplasia molecular diagnosis |
| title | Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach |
| title_full | Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach |
| title_fullStr | Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach |
| title_full_unstemmed | Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach |
| title_short | Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach |
| title_sort | molecular diagnosis of steroid 21 hydroxylase deficiency a practical approach |
| topic | ccongenital adrenal hyperplasia (CAH) 21-hydroxylase deficiency CYP21A2 gene classical forms of congenital adrenal hyperplasia non-classical forms of congenital adrenal hyperplasia molecular diagnosis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.834549/full |
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