ACTH resistance syndromes.
Inherited adrenocorticotropin (ACTH) insensitivity syndromes comprise a group of rare diseases in which resistance to ACTH is either the sole feature or associated with other symptoms. This review focuses on two autosomal recessive disorders, familial glucocorticoid deficiency (FGD) (MIM*202200) and the triple A syndrome (MIM*231550), which have at least three different molecular aetiologies. In FGD, several missense mutations within the coding region of the ACTH receptor (MC2-R) have been identified in some, but not all patients, and segregation analyses and functional studies in a Y6 cell expression system confirmed that these mutations cause the disease. Some cases of FGD are not linked to the MC2-R locus on chromosome 18p11.2 suggesting genetic heterogeneity. The triple A syndrome is clinically characterized by the triad of adrenal insufficiency, achalasia and alacrima and a variety of neurological symptoms. After excluding several candidate genes we mapped this syndrome to a 6 cM interval on chromosome 12q13 with no indication for genetic heterogeneity. The identification of the gene(s) causing FGD without mutations in the MC2-R and causing the triple A syndrome may reveal novel aspects in cell signalling and neuroendocrinology.
Huebner
A
A
Children's Hospital, Technical University Dresden, Germany.
Elias
L L
LL
Clark
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000502:physiology*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003001:Cloning, Molecular; D004351:Drug Resistance / Q000235:genetics; D018740:Genetic Heterogeneity; D005938:Glucocorticoids / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D018043:Receptors, Corticotropin / Q000235:genetics* / Q000502:physiology; D013577:Syndrome
D005938:Glucocorticoids; D018043:Receptors, Corticotropin; D000324:Adrenocorticotropic Hormone