Mutation in the CYP21B gene (Ile-172. -->. Asn) causes steroid 21-hydroxylase deficiency

Journal Article · Tue Mar 01 00:00:00 EST 1988 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.85.5.1600· OSTI ID:6618472

Amor, M; Parker, K L; Globerman, H; New, M I; White, P C

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. It results from a deficiency in a specific cytochrome P450, P450c21 (P450XXIA). The gene encoding this protein (CYP21B) and a closely linked pseudogene (CYP21A) are located in the HLA complex on chromosome 6p. Many mutant alleles are associated with deletions of CYP21B; the authors report the cloning and characterization of a nondeleted mutant CYP21B gene. This mutant gene is expressed on transfection into mouse Y1 adrenal cells, producing mRNA levels similar to those seen after transfection of the normal CYP21B gene. In codon 172 of the mutant gene, the normal codon ATC, encoding isoleucine, has been changed to AAC, encoding asparagine. This mutation is normally present in the CYP21A pseudogene, so that it may have been transferred to the mutant CYP21B gene by gene conversion. Hybridization of oligonucleotide probes corresponding to this and two other mutations normally present in CYP21A demonstrated that 4 out of 20 patients carried the codon 172 mutation; in one of these patients, the mutation was present as part of a larger gene conversion involving at least exons 3-6. Gene conversion may be a frequent cause of 21-hydroxylase deficiency.

• Research Organization: Cornell Univ. Medical Center, New York, NY (USA)
• OSTI ID: 6618472
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 85:5
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HEREDITARY DISEASES
PATHOGENESIS
HYDROXYLASES
MUTATIONS
ADRENAL GLANDS
ASPARAGINE
CHROMOSOMAL ABERRATIONS
CYTOCHROMES
GENES
HYBRIDIZATION
LEUCINE
MESSENGER-RNA
MUTAGENESIS
OLIGONUCLEOTIDES
STEROIDS
AMIDES
AMINO ACIDS
BODY
CARBOXYLIC ACIDS
DISEASES
ENDOCRINE GLANDS
ENZYMES
GLANDS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PIGMENTS
PROTEINS
RNA
550401* - Genetics- Tracer Techniques