No evidence of mutations in the genes for type I and type II 3{beta}-hydroxysteroid dehydrogenase (3{beta}HSD) in nonclassical 3{beta}HSD deficiency
- New York Hospital-Cornell Medical Center, New York, NY (United States); and others
Nonclassical 3{beta}-hydroxysteroid dehydrogenase/{Delta}{sup 5}-{Delta}{sup 4}-isomerase deficiency (NC3{beta}HSDD) has been diagnosed in hyperandrogenic women with an increasing frequency during the last 14 yr. Fifteen menarcheal women with androgen excess syndrome, previously diagnosed with NC3{beta}HSDD were studied, in 12 after discontinuation of glucocorticoid treatment, in 2 patients never treated with glucocorticoids, and in 1 both before and after glucocorticoid therapy. Molecular DNA analysis was also performed in 6 of the patients, using the strategy successfully used to detect point mutations in the type II 3{beta}-hydroxysteriod dehydrogenase (3{beta}HSD) gene, which are responsible for classical 3{beta}HSD deficiency. This strategy consists of the direct sequencing of polymerase chain reaction-amplified DNA fragments corresponding to the complete coding sequence and all intron-exon junctions and to the 5{prime}- and 3{prime}-noncoding region of this gene. We were unable to demonstrate any mutation of the type II 3{beta}HSD gene in these 6 patients. To gain additional information about potential mutations, direct sequencing of the type I 3{beta}HSD gene was also performed using this same strategy, and no mutations were found. The present study strongly suggests that unlike the salt-losing and nonsalt-losing forms of classical 3{beta}HSD deficiency, NC3{beta}HSDD is not due to a mutant type II 3{beta}HSD enzyme. However, the possibility remains of a mutation(s) in the unsequenced regions of the type II 3{beta}HSD gene or elsewhere, such as in a gene for modulatory protein, playing a specific role in the expression of the type II 3{beta}HSD gene. On the other hand, knowing the multiple hormonal controls to which 3{beta}HSD activity is subject, it cannot be excluded that at least in some cases, NC3{beta}HSDD may be an acquired defect, the result of endogenous or environmental factors. 41 refs., 2 figs., 2 tabs.
- OSTI ID:
- 183229
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism, Vol. 79, Issue 6; Other Information: PBD: Dec 1994
- Country of Publication:
- United States
- Language:
- English
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