[Familial glucocorticoid deficiency due to the ACTH receptor gene mutations]

Abstract

Familial glucocorticoid deficiency(FGD) is a rare autosomal recessive disorder, characterized by resistance to ACTH leading to glucocorticoid deficiency, but not mineralocorticoid deficiency. Recently, mutations in the ACTH receptor gene were identified in several families with FGD. Thus far, twelve missense mutations, one nonsense mutation and three frameshift mutations causing FGD were described. Functional expression studies demonstrated that most of the missense mutations results in loss of specific binding to ACTH and impaired production of cAMP in response to ACTH. However, the genotype-phenotype correlation was poor. Interestingly and unexpectedly, the FGD patients with the ACTH receptor gene mutations were shown to be tall.