IDENTIFICATION OF THE CYS634-]TYR MUTATION OF THE RET PROTOONCOGENE IN A PEDIGREE WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-2A AND LOCALIZED CUTANEOUS LICHEN AMYLOIDOSIS

Following the recent identification of specific germline mutations of the RET proto-oncogene in Multiple Endocrine Neoplasia type 2A (MEN2A) patients, we looked for mutations of this gene in a pedigree showing recurrence of MEN2A and localized Cutaneous Lichen Amyloidosis (CLA). Basal calcitonin and/or pentagastrin test performed in all the 10 avai lable members of this pedigree confirmed the clinical diagnosis and al lowed the presymptomatic identification of an additional carrier. A cy s634->tyr missense mutation, already reported as causative in MEN2A pa tients, was identified after SSCP analysis and direct sequencing of ex on 11 of the RET proto-oncogene in one individual affected with both M EN2A and CLA, thus suggesting a common etiology for the two disorders. Taking advantage of the observation of an RsaI restriction site in th e sequence surrounding the mutated codon, we could demonstrate that th e same mutation is present in three other affected members, in the pre symptomatic carrier and in one additional 25 years old healthy member who shows a mildly positive pentagastrin test.