The molecular basis of adrenocorticotrophin resistance syndrome.
Adrenocorticotrophin resistance syndromes comprise familial glucocorticoid deficiency (FGD) and triple A syndrome, which are rare autosomal recessive diseases with distinct clinical features and molecular etiologies. Mutations of melanocortin-2 receptor (MC2R) have been described in segregation with FGD in 25% of patients. More recently melanocortin-2 receptor accessory protein (MRAP), a small single-transmembrane domain protein, was described as an essential protein for the traffic of MC2R and its expression on the plasma membrane. About 20% of FGD patients carry homozygous mutations of MRAP. The ALADIN protein (for alacrima/achalasia/adrenal insufficiency/neurologic disorder) was identified as the molecular basis of triple A syndrome. The elucidation of the genetic basis of the ACTH resistance syndrome has contributed to the better understanding of MC2R function. However, in some patients the molecular etiology is not yet known and awaits further genetic studies.
Elias
Lucila L K
LL
Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
Clark
Adrianj L
AL
D000309:Adrenal Insufficiency / Q000150:complications / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D004931:Esophageal Achalasia / Q000150:complications / Q000235:genetics; D005938:Glucocorticoids / Q000172:deficiency; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics
D005938:Glucocorticoids; D008565:Membrane Proteins; D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone