EXCLUSION OF THE ADRENOCORTICOTROPIN (ACTH) RECEPTOR (MC2R) LOCUS IN SOME FAMILIES WITH ACTH RESISTANCE BUT NO MUTATIONS OF THE MC2R CODINGSEQUENCE (FAMILIAL GLUCOCORTICOID DEFICIENCY TYPE-2)

Several mutations in the coding exon of the ACTH receptor (MC2R) gene have been reported Fn cases of familial glucocorticoid deficiency or F GD. However, many patients with a similar syndrome do not present any mutation in the coding region of this gene. This is the case in II fam ilies we have investigated. Patients in these families present the typ ical clinical features of FGD, but no mutation was found in the coding exon of the ACTH receptor. To determine whether mutations on MC2R gen e, but outside the coding region, mag be involved in FGD in these fami lies, we have performed a linkage analysis. Using three markers flanki ng MC2R gene on chromosome 18, me ii ere able to exclude linkage in a region of 12 centimorgans around the gene. This result clearly indicat es that FGD is genetically heterogeneous. Defects in gene(s) different from MC2R gene are implicated in this syndrome.