title: [Mutations in 21-hydroxylase gene caused by gene conversion-like events].
abstract: Two steroid 21-hydroxylase genes (CYP21A and CYP21B) alternate in tandem with two genes for the fourth component of complement (C4A and C4B) on the short arm of chromosome 6 between the loci of HLA-B and HLA-DR. The CYP21B gene encodes an adrenal microsomal cytochrome P-450, which is specific for steroid 21-hydroxylation (P450c21). A defect of this protein would cause 21-hydroxylase deficiency, which is an autosomal recessive disease and is the most common cause of congenital adrenal hyperplasia (CAH). On the other hand, the CYP21A gene, which is homologous to the CYP21B gene up to 98% in the nucleotide sequences, is a pseudogene due to several mutations in the coding region. One of the mutations is a C----T change leading a termination codon, TAG, in the 8th exon. 1) I cloned a CYP21B gene from a patient homozygous for HLA-Bw75-DRw9 by descent. I found a C----T change in the 8th exon of the CYP21B gene. This mutation would prevent a synthesis of 21-hydroxylase and was thought to be a crucial change to cause CAH in this patient. Because there was no apparent gross change in the organization of the C4-CYP21 region and this mutation is usually found in the CYP21A pseudogene, it seemed that a gene conversion-like event transferred the mutation from the CYP21A gene to the CYP21B gene. 2) A population study on the organization of C4-CYP21 region revealed that a reciprocal change, i.e. a T----C change in the 8th exon of the CYP21A gene, was observed in two HLA haplotypes, HLA-B44-DRw13 and HLA-Bw46-DRw8 haplotypes in Japanese population. The reciprocal changes also may be considered as a result of gene conversion-like events.
authors.affiliation: Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka.
authors.forename: K
authors.initials: K
authors.lastname: Urabe
mesh_terms: D005785:Gene Conversion; D005828:Genetics, Population; D006801:Humans; D007564:Japan; D009154:Mutation; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase