Gene conversion-like events cause steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia

Proc Natl Acad Sci U S A. 1987 Nov;84(22):8091-4. doi: 10.1073/pnas.84.22.8091.

Abstract

Genomic DNAs from twelve Japanese patients with steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10] deficiency were analyzed by Southern blot hybridization. A 3.7-kilobase (kb) Taq I and a 1.7-kb Pvu II restriction endonuclease fragment that correspond to a 21-OHase B gene were absent from the DNA of two unrelated patients with the salt-wasting form of the disease. However, a 10.5-kb Bgl II fragment corresponding to the region encompassing the 21-OHase B gene was still present in these two patients. The genes encoding 21-OHase were cloned from one of these two patients, who was homozygous by descent for HLA-A26;B39;C4A3;C4B1;DR4. Restriction endonuclease mapping as well as partial nucleotide sequencing analysis revealed that the 21-OHase B gene of the patient has been converted to the pseudogene, 21-OHase A, as far as the critical 0.5-kb sequence was concerned. Thus, the defect was due to both chromosomes each carrying two copies of 21-OHase A pseudogene and lacking functional 21-OHase B gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital* / enzymology
  • Adrenal Hyperplasia, Congenital* / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • DNA / analysis
  • Gene Conversion*
  • Genes
  • Humans
  • Japan
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Pseudogenes*
  • Steroid 21-Hydroxylase / genetics
  • Steroid Hydroxylases / deficiency*

Substances

  • DNA
  • Steroid Hydroxylases
  • Steroid 21-Hydroxylase

Associated data

  • GENBANK/J02981