Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products
Open accessAbstract
Four steroid 21-hydroxylase B [P-450(C21)B] genes (designated P.7, P.10-1, P.10-2, and P.3) from three P-450(C21)-deficient patients were isolated to analyze their structures and functions. Several base changes were observed in the sequences of the four P-450(C21)B genes as compared to that of the functional B gene. Many of these base changes were identical to those of the P-450(C21)A pseudogene. The three DNAs (P.10-1, P.10-2, and P.3) produced no P-450(C21) activity in a functional assay for P-450(C21) by the COS cell expression system, while the P.7 DNA expressed the activity. The P.10-1 and P.10-2 DNAs were shown to have a point mutation in the second intron, causing aberrant splicing. The P.3 DNA carried three clustered missense mutations in the sixth exon, which impaired P-450(C21) activity. All these critical mutations could be seen in the corresponding site of the P-450(C21)A pseudogene. These data strongly suggest the involvement of gene conversion in this genetic disease.
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- Authors
- Higashi, Y., Tanae, A., Inoue, H., Hiromasa, T., & Fujii-Kuriyama, Y.
- Affiliations
- Department of Biochemistry, Cancer Institute, Tokyo, Japan.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1988-10
- Volume
- 85
- Issue
- 20
- Pages
- 7486-7490
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC282216
- OpenAlex
- W2047088170
- Cited by
- 244
- References
- 23
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 1 · 2017: 1 · 2016: 7 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- 21-hydroxylase deficiency, CYP21, gene conversion, aberrant splicing, missense mutations, congenital adrenal hyperplasia, clustered mutations, gene structure
- MeSH terms
- Adrenal Hyperplasia, Congenital, Base Sequence, Cell Line, Cloning, Molecular, DNA, Endonucleases, Exons, Gene Conversion, Gene Expression Regulation, Humans, Introns, Molecular Sequence Data, Mutation, RNA Splicing, RNA, Messenger, Steroid Hydroxylases, Steroid 21-Hydroxylase, Single-Strand Specific DNA and RNA Endonucleases
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