title: Nonsense mutation causing steroid 21-hydroxylase deficiency.
abstract: We determined the sequence of a mutant CYP21B gene isolated from a patient with the severe, "salt-wasting" form of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Codon 318 in this gene is changed from CAG, encoding glutamine, to TAG, a nonsense codon. This is predicted to result in a completely nonfunctional enzyme due to premature termination of translation. In addition, when the cloned mutant gene was transfected into mouse Y1 adrenal cells, the resulting mRNA levels were decreased compared with transfected normal CYP21B genes. This mutation was carried by 3 of 20 unrelated patients with 21-hydroxylase deficiency alleles as determined by hybridization with a specific oligonucleotide probe. This mutation is also seen in the normal CYP21A pseudogene, so that its presence in the abnormal CYP21B gene may be the result of a gene conversion event.
authors.affiliation: Division of Pediatric Endocrinology, Cornell University Medical College, New York 10021.
authors.forename: H
authors.initials: H
authors.lastname: Globerman
authors.forename: M
authors.initials: M
authors.lastname: Amor
authors.forename: K L
authors.initials: KL
authors.lastname: Parker
authors.forename: M I
authors.initials: MI
authors.lastname: New
authors.forename: P C
authors.initials: PC
authors.lastname: White
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000235:genetics; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D014162:Transfection
chemical_list: D003062:Codon; D009841:Oligonucleotides; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase