Characterization of frequent deletions causing steroid 21-hydroxylase deficiency

White, P C; Vitek, A; Dupont, B; New, M I

doi:10.1073/pnas.85.12.4436

Cited by 230Sexual Differentiation and DisordersAdrenal Hormones and DisordersGenomic variations and chromosomal abnormalities

Characterization of frequent deletions causing steroid 21-hydroxylase deficiency

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White, P C, Vitek, A, Dupont, B, New, M I·1988·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.85.12.4436PMC PMC280444

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Abstract

Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21B gene. This gene and a highly homologous pseudogene, CYP21A, alternate with the C4A and C4B genes encoding the fourth component of complement. Classical deficiency alleles are frequently caused by deletions of CYP21B or by gene conversions that transfer deleterious mutations from the CYP21A pseudogene to CYP21B. Gene conversions involving restriction enzyme sites that distinguish CYP21A [e.g., 3.2-kilobase (kb) Taq I fragment] and CYP21B (3.7-kb Taq I fragment) might be confused with actual deletions of CYP21B. To determine the incidence of this type of gene conversion, 15 chromosomes (in 13 families) with absent 3.7-kb Taq I fragments were studied. When hybridized with a 21-hydroxylase probe, all of these chromosomes were associated with absent 2.9-kb Kpn I fragments, 14 of 15 were associated with absent 2.4-kb Bgl II/EcoRI fragments, and 13 of 15 were associated with absent 10-kb Bgl II/EcoRI and 12-kb EcoRI fragments. Thirteen of 15 chromsomes had absent 6.0- or 5.4-kb Taq I fragments when hybridized with a C4 probe. Thus, 2 of 15 chromosomes do not carry deletions and may represent gene conversions; 13 of 15 chromosomes studied have a deletion of approximately equal to 30 kb, leaving behind the C4A gene and a single CYP21A-like gene. Hybridization with specific oligonucleotide probes showed that in all 13 cases this remaining CYP21 gene carried an 8-base-pair deletion, typical of CYP21A, that prevents synthesis of a functional protein. Thus, gene conversions are rarely confused with deletions as a cause of 21-hydroxylase deficiency.

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Authors: White, P. C., Vitek, A., Dupont, B., & New, M. I.
Affiliations: Cornell University (US)
ORCID: White, P C
Dupont, B
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1988-06
Volume: 85
Issue: 12
Pages: 4436-4440
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.85.12.4436
PMC: PMC280444
OpenAlex: W1986580467
Cited by: 229
References: 26
Citations by year: 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 7 · 2012: 4
FWCI: 4.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Cancer Institute (CA 22507)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-37867)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 00072)
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 › Genomic variations and chromosomal abnormalities
Keywords: 21-hydroxylase deficiency, gene conversion, congenital adrenal hyperplasia
MeSH terms: Adrenal Hyperplasia, Congenital, Chromosome Deletion, Female, Gene Conversion, Genes, Haplotypes, Humans, Male, Nucleic Acid Hybridization, Plasmids, Steroid Hydroxylases, Steroid 21-Hydroxylase

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Characterization of frequent deletions causing steroid 21-hydroxylase deficiency

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