The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene
Open accessAbstract
Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency. The cDNA and gene of the human ACTH receptor were recently cloned. The gene encodes a 297-amino acid protein that belongs to the G protein-coupled superfamily of membrane receptors. We hypothesized that the ACTH receptor gene might be defective in IGD. To examine this, we studied its genomic structure by PCR and direct sequencing in a 5-yr-old proband with the disease, his parents, and grandparents. The proband was a compound heterozygote for two different point mutations, one in each allele: (a) a substitution (C-->T), also found in one allele of the mother and maternal grandmother, which introduced a premature stop codon (TGA) at position 201 of the protein; this mutant receptor lacks its entire carboxy-terminal third and, if expressed, should be unable to transduce the signal; and (b) a substitution (C-->G), also found in one of the paternal alleles, which changed neutral serine120 in the apolar third transmembrane domain of the receptor to a positively charged arginine, probably disrupting the ligand-binding site. Standard ovine corticotropin releasing hormone (oCRH) test in the heterozygote parents and maternal grandmother revealed exaggerated and prolonged ACTH responses, suggestive of subclinical resistance to ACTH. We conclude that IGD in this family appears to be due to defects of the ACTH receptor gene. The oCRH test appears to be useful in ascertaining heterozygosity in this syndrome.
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“Patients with inactivating mutations in the ACTH receptor (MC2R) (159) or the LH/hCG receptor (160) make negligible steroids from the affected glands.”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [159]
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The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
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Metadata
- Authors
- Tsigos, C., Arai, K., Hung, W., & Chrousos, G. P.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1993-11-01
- Volume
- 92
- Issue
- 5
- Pages
- 2458-2461
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288430
- OpenAlex
- W2055723678
- Semantic Scholar
- ba08231d871519ab7bf0f7184b630e96181458b1
- Cited by
- 182
- References
- 21
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Addison's disease, compound heterozygosity, G protein-coupled receptors, premature stop codon, ACTH resistance, autosomal recessive inheritance
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Amino Acid Sequence, Base Sequence, Child, Preschool, Female, Genes, Recessive, Glucocorticoids, Heterozygote, Homozygote, Humans, Hydrocortisone, Lipid Metabolism, Inborn Errors, Male, Molecular Sequence Data, Pedigree, Genome, Human, Point Mutation, Sequence Analysis, DNA, Receptors, Corticotropin
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