Deletion hybrid genes, due to unequal crossing over between CYP11B1 (11beta-hydroxylase) and CYP11B2(aldosterone synthase) cause steroid 11beta-hydroxylase deficiency and congenital adrenal hyperplasia
| Autor: | S, Portrat, P, Mulatero, K M, Curnow, J L, Chaussain, Y, Morel, L, Pascoe |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
DNA Complementary Adrenal Hyperplasia Congenital Cortodoxone Homozygote Androstenedione Gene Expression Puberty Precocious Exons Transfection Polymerase Chain Reaction Blotting Southern Child Preschool COS Cells Renin Animals Cytochrome P-450 CYP11B2 Humans Steroid 11-beta-Hydroxylase Crossing Over Genetic Cyproterone Acetate Promoter Regions Genetic Aldosterone Gene Deletion |
| Popis: | Chromosomal rearrangements are natural experiments that can provide unique insights into in vivo regulation of genes and physiological systems. We have studied a patient with congenital adrenal hyperplasia and steroid 11beta-hydroxylase deficiency who was homozygous for a deletion of the CYP11B1 and CYP11B2 genes normally required for cortisol and aldosterone synthesis, respectively. The genes were deleted by unequal recombination between the tandemly arranged CYP11B genes during a previous meiosis, leaving a single hybrid gene consisting of the promoter and exons 1-6 of CYP11B2 and exons 7-9 of CYP11B1. The hybrid gene also carried an I339T mutation formed by intracodon recombination at the chromosomal breakpoint. The mutant complementary DNA corresponding to this gene was expressed in COS-1 cells and was found to have relatively unimpaired 11beta-hydroxylase and aldosterone synthase activities. Apparently the 11beta-hydroxylase deficiency and the adrenal hyperplasia are due to the lack of expression of this gene in the adrenal zona fasciculata/reticularis resulting from replacement of the CYP11B1 promoter and regulatory sequences by those of CYP11B2. |
| Databáze: | OpenAIRE |
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