Familial bilateral macronodular adrenal hyperplasia due to a new ARMC 5 germline mutation. Clinical status and possible association with other neoplasms.

Abstract

Abstract Mutations in the ARMC5 gene (armadillo repeat containing 5, OMIM 615549), a putative tumor suppression gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (HAMB). HAMB in familial cases is believed to be determined by two mutations, one germinal and the other somatic, as pointed out by the theory of the 2 hits. We present an affected family with 11 members carrying a new mutation of the ARMC5 gene (NM_001288767.1): c.2162T > C p. (Leu721Pro). Two of the carrier patients developed clinical Cushing Syndrome (CS), two possible autonomous cortisol secretion (ACS) and 1 presented with autonomous cortisol secretion (ACS). Four patients suffered from malignant neoplasms. Three of them died from these tumors.