Work

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

Year: 1991

Type: article

Abstract: Congenital lipoid adrenal hyperplasia is the most severe form of congenital adrenal hyperplasia.Affected individuals can syn- thesize no steroid hormones, and hence are all phenotypic females with a severe salt-losing syndrome that is fatal if not treated in early infancy.All previous studies have suggested that the disorder is in the cholesterol side chain cleavage en- zyme (P450scc), which converts cholesterol to pregnenolone.A newborn patient was diagnosed by the lack of significant con- centrations of adrenal or gonadal steroids either before or after stimulation with corticotropin (ACTH) or gonadotropin (hCG).The P450scc gene in this patient and in a previously described patient were grossly intact, as evidenced by Southern blotting patterns.Enzymatic (polymerase chain reaction) amplification and sequencing of the coding regions of their P450scc genes showed these were identical to the previously cloned human P450scc cDNA and gene sequences.Undetected compound he- terozygosity was ruled out in the new patient by sequencing P450scc cDNA enzymatically amplified from gonadal RNA.Northern blots of gonadal RNA from this patient contained normal sized mRNAs for P450scc and also for adrenodoxin reductase, adrenodoxin, sterol carrier protein 2, endozepine, and GRP-78 (the precursor to steroidogenesis activator pep- tide).These studies show that lipoid CAH is not caused by lesions in the P450scc gene, and suggest that another unidentified factor is required for the conversion of cholesterol to preg- nenolone, and is disordered in congenital lipoid adrenal hyperplasia.(J.Clin.Invest.1991Invest..88:1955Invest.-1962.)Key words: preg- nenolonepseudohermaphroditism * cholesterol desmolasepolymerase chain reaction * sex steroids probe Southern blots of DNA from three patients and various controls, finding no deletions, rearrangements, or restriction Congenital Lipoid Adrenal Hyperplasia 1955

Source: Journal of Clinical Investigation

DOI: 10.1172/jci115520

Authors: D Lin, S E Gitelman, P Saenger, W L Miller

Institutions: University of California, San Francisco, Albert Einstein College of Medicine

Language: English

Topic: Sexual Differentiation and Disorders

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze