@article{3054199,
    title = "Mutations of the ACTH receptor gene in a new family with isolated
glucocorticoid deficiency",
    author = "Tsigos, C and Tsiotra, P and Garibaldi, LR and Stavridis, JC and and Chrousos, GP and Raptis, SA",
    journal = "Molecular Genetics and Metabolism",
    year = "2000",
    volume = "71",
    number = "4",
    pages = "646-650",
    publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
    issn = "1096-7192, 1096-7206",
    doi = "10.1006/mgme.2000.3090",
    keywords = "ACTH receptor; ACTH resistance; adrenal insufficiency; glucocorticoid
deficiency; G-protein-coupled receptors",
    abstract = "Isolated glucocorticoid deficiency (IGD) is an autosomal recessive
disorder characterized by primary adrenocortical insufficiency, without
mineralocorticoid deficiency. Mutations of the ACTH receptor gene have
been reported in several families with IGD. We have amplified and
directly sequenced the entire intronless ACTH receptor gene in a new
family with IGD. The proband was found to be compound heterozygote for
two different point mutations, one in each allele: (a) a substitution
(360C>G) which changed neutral serine at position 120 in the apolar
third transmembrane domain of the receptor to a positively charged
arginine (S120R), probably disrupting the ligand-binding site; and (b) a
substitution (761A>G) changing tyrosine at position 254 to cysteine
(Y254C) in the third extracellular loop of the receptor protein, that
also likely disrupts its structure and interferes with ligand binding.
Each of the two mutations in the proband has previously been described
in a different family, S120R in compound heterozygosity with a stop
codon (R201X) and Y254C in homozygote form. Thus, in the absence of in
vitro functional studies, our findings confirm the pathogenetic role of
the S120R and Y254C mutants in the development of resistance to ACTH.
(C) 2000 Academic Press."
}