Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin

Familial glucocorticoid deficiency due to corticotropin (ACTH) resistance consists of two distinct genetic syndromes that are both inherited as autosomal recessive traits: isolated ACTH resistance (iACTHR), which may be caused by inacti-vating mutations of the ACTH receptor (the MC2R gene) or mutations in an as yet unknown gene(s), and Allgrove syn-drome (AS). The latter is also known as triple-A syndrome (MIM 231550). In three large cohorts of AS kindreds, the dis-ease has been mapped to chromosome 12; most recently, mu-tations in the AAAS gene on 12q13 were found in these AS families. AAAS codes for the WD-repeat containing ALADIN (for alacrima-achalasia-adrenal insufficiency-neurologic dis-order) protein. We investigated families with iACTHR (n 4) and AS (n 6) and a Bedouin family with ACTHR and a known defect of the TSH receptor. Four AS families were of mixe