title: Gene conversion-like events cause steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia.
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.
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D005785:Gene Conversion; D005796:Genes; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011544:Pseudogenes; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000172:deficiency*
chemical_list: D004247:DNA; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase