CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants
Open accessAbstract
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis. Disorders in steroid 21-hydroxylation account for over 95% of patients with CAH. Clinically, the 21-hydroxylase deficiency has been classified in a broad spectrum of clinical forms, ranging from severe or classical, to mild late onset or non-classical. Known allelic variants in the disease causing CYP21A2 gene are spread among different sources. Until recently, most variants reported have been identified in the clinical setting, which presumably bias described variants to pathogenic ones, as those found in the CYPAlleles database. Nevertheless, a large number of variants are being described in massive genome projects, many of which are found in dbSNP, but lack functional implications and/or their phenotypic effect. In this work, we gathered a total of 1,340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have an effect on human health, and compiled all this information in an integrated database. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations, including double mutants in cis. Data compiled in the present work could help physicians in the genetic counseling of families affected with 21-hydroxylase deficiency.
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Over 300 pathogenic variants have been identified in CYP21A2, including point pathogenic variants, small insertions/deletions, and large structural rearrangements.
“To date, over 300 pathogenic variants have been identified in CYP21A2, including point pathogenic variants, small insertions/deletions, and large structural rearrangements (23).”
From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [23]
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“To date, over 300 pathogenic variants have been identi fi ed in CYP21A2 , including point pathogenic variants, small insertions/deletions, and large structural rearrangements (23).”
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Self-citation
- Authors
- Simonetti, L., Bruque, C. D., Fernández, C. S., Benavides-Mori, B., Delea, M., Kolomenski, J. E., Espeche, L. D., Buzzalino, N. D., Nadra, A. D., & Dain, L.
- Affiliations
- Administración Nacional de Laboratorios e Institutos de Salud (AR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Centro Nacional de Genética Médica; ANLIS; Buenos Aires Argentina
- Corresponding author
- Nadra, Alejandro D.
- ORCID
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2017-11-06
- Volume
- 39
- Issue
- 1
- Pages
- 5-22
- ISSN
- 1059-7794 (ISSN-L)
- OpenAlex
- W2767052015
- Cited by
- 122
- References
- 20
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 37 · 2023: 12 · 2022: 12 · 2021: 19 · 2020: 8 · 2019: 10 · 2018: 4
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- Agencia Nacional de Promoción Científica y Tecnológica
- Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2013 11220130100542, 2013 11220130100542)
- Universidad de Buenos Aires (20020110100005BA)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- CYP21A2, congenital adrenal hyperplasia, 21-hydroxylase deficiency, genetic variants, variant database, dbSNP, double mutants, genetic counseling
- MeSH terms
- Adrenal Hyperplasia, Congenital, Alleles, Genotype, Humans, Mutation, Phenotype, Steroid 21-Hydroxylase, Genetic Variation, Databases, Genetic, Genetic Association Studies
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