Cited by 244Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products

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Higashi, Y, Tanae, A, Inoue, H, Hiromasa, T, Fujii-Kuriyama, Y·1988·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.85.20.7486

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Authors
Higashi, Y., Tanae, A., Inoue, H., Hiromasa, T., & Fujii-Kuriyama, Y.
Affiliations
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Venue
Proceedings of the National Academy of Sciences
Published
1988-10
Volume
85
Issue
20
Pages
7486-7490
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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