Characterization of frequent deletions causing steroid 21-hydroxylase deficiency

Journal Article · Wed Jun 01 04:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.12.4436· OSTI ID:5563642

White, P C; Vitek, A; Dupont, B; New, M I ^[1]

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1. Cornell Univ. Medical College, New York, NY (USA)

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 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 chromosomes 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 {approx}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.

• OSTI ID: 5563642
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:12; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CONSTITUENTS
CHROMOSOMAL ABERRATIONS
COMPLEMENT
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
ENZYMES
GENE MUTATIONS
GENE RECOMBINATION
HEREDITARY DISEASES
HUMAN POPULATIONS
HYBRIDIZATION
HYDROXYLASES
ISOTOPES
LIGHT NUCLEI
MOLECULAR BIOLOGY
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
POPULATIONS
PROTEINS
RADIOISOTOPES
STEROIDS