Nonsense mutation causing steroid 21-hydroxylase deficiency

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 pred...

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Bibliographic Details
Published in:The Journal of clinical investigation 1988-07, Vol.82 (1), p.139-144
Main Authors: GLOBERMAN, H, AMOR, M, PARKER, K. L, NEW, M. I, WHITE, P. C
Format: Article
Language:English
Subjects:
Adrenal Hyperplasia, Congenital - enzymology
Adrenal Hyperplasia, Congenital - etiology
Adrenal Hyperplasia, Congenital - genetics
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Codon - genetics
Genes
Humans
Medical genetics
Medical sciences
Molecular Sequence Data
Mutation
Nucleic Acid Hybridization
Oligonucleotides - genetics
Steroid 21-Hydroxylase - genetics
Steroid Hydroxylases - genetics
Transfection
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI113562