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Cited by 120Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

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

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Lin, D, Gitelman, S E, Saenger, P, Miller, W L·1991·Journal of Clinical Investigation
DOI 10.1172/jci115520
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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

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  • Studies of DNA from affected patients revealed that CYP11A1 gene encoding P450scc was normal, and in 1995 disease was termed 'congenital lipoid adrenal hyperplasia (lipoid CAH)', caused by mutations in StAR.

    “However, studies of DNA from affected patients revealed that the CYP11A1 gene encoding P450scc was normal21,22,23,24), and in 1995 this disease was more properly termed 'congenital lipoid adrenal hyperplasia (lipoid CAH)', and it was caused by mutations in the gene encoding StAR3,25).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [22]

  • The gene for P450scc is normal in patients with lipoid CAH, as are the mRNAs for adrenodoxin reductase and adrenodoxin.

    “However, the gene for P450scc is normal in these patients (102), as are the mRNAs for adrenodoxin reductase and adrenodoxin (102).”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [102]

  • The normal P450scc system plus the accumulation of cholesterol esters in the affected adrenal suggested that the lesion lay in an upstream factor involved in cholesterol transport into mitochondria.

    “The normal P450scc system plus the accumulation of cholesterol esters in the affected adrenal suggested that the lesion lay in an upstream factor involved in cholesterol transport into mitochondria (102).”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [102]

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  1. [25]25. New, M. I., P. C. White, S. Pang, B. Dupont, and P. W. Speiser. 1989. The adrenal hyperplasias. In The Metabolic Basis of Inherited Disease. 6th ed. C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, editor. McGraw-Hill Book Co., New York. 1881-1917.
  2. [52]52. Schmitz, G., and G. Assman. 1989. Acid lipase deficiency: Wolman's disease and cholesteryl ester storage disease. In The Metabolic Basis of Inherited Disease. 6th ed. C. R. Scrirer, A. L. Beaudet, W. S. Sly, and D. Valle, editors. McGraw-Hill Book Co., New York. 1623-1644. 1962

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Authors
Lin, D., Gitelman, S. E., Saenger, P., & Miller, W. L.
Affiliations
  • University of California, San Francisco (US)
  • Albert Einstein College of Medicine (US)
ORCID
Miller, W L
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1991-12-01
Volume
88
Issue
6
Pages
1955-1962
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci115520
OpenAlex
W2051890768
Semantic Scholar
2937b8a36acf8fd381c089d0afcdc9e41caca86c
Cited by
120
References
47
Citations by year
2025: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2014: 5 · 2013: 3 · 2012: 2
FWCI
1.98
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • March of Dimes Foundation
  • University of Pennsylvania
  • Northwestern University
  • National Institutes of Health (5r01dk042154-09)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, DK 42154, R01DK037922)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
congenital lipoid adrenal hyperplasia, cholesterol side-chain cleavage enzyme, P450scc, congenital adrenal hyperplasia, steroidogenesis, pregnenolone, adrenodoxin reductase, adrenodoxin, sterol carrier protein 2, endozepines, GRP78
MeSH terms
Adrenal Hyperplasia, Congenital, Adrenocorticotropic Hormone, Base Sequence, Cholesterol Side-Chain Cleavage Enzyme, DNA, Female, Humans, Infant, Newborn, Molecular Sequence Data, RNA, Messenger, Polymerase Chain Reaction

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