Abstract
Familial glucocorticoid deficiency is an uncommon disorder that mimics childhood Addison's disease but with preserved mineralocorticoid function. We have postulated that it might result from defective ACTH receptor function. We studied a patient with this condition using the technique of polymerase chain reaction (PCR) to amplify the ACTH receptor from his genomic DNA using primers based on the sequence of the recently reported ACTH receptor DNA sequence. PCR products were subcloned in plasmids and sequenced using the dideoxy chain termination technique. We consistently found a single base change (G > T) in codon 74 resulting in the substitution of Isoleucine for Serine. This mutation destroys a Fnu4H1 restriction site which facilitates the study of first degree relatives. Using this restriction site polymorphism we identified the proband and his similarly affected sister as being homozygous mutants, an unaffected brother as being a normal homozygote, and both parents as being heterozygotes for the same mutation. Serine 74 lies in the second transmembrane domain of this receptor and is conserved amongst all members of the ACTH/MSH/ cannabinoid receptor family, and thus it appears to play an important part in the recognition of MSH peptides. The study of other families with this syndrome and expression and mutation studies with this receptor should allow us to define more clearly the nature of this interaction.
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Clark, A., Weber, A., Grossman, A. et al. A POINT MUTATION OF THE ACTH RECEPTOR IN FAMILIAL GLUCOCORTICOID DEFICIENCY. Pediatr Res 33 (Suppl 5), S14 (1993). https://doi.org/10.1203/00006450-199305001-00067
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DOI: https://doi.org/10.1203/00006450-199305001-00067