EXCLUSION OF THE PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-BETA-3 (PLCB3) GENE AS A CANDIDATE FOR MULTIPLE ENDOCRINE NEOPLASIA TYPE-1

The predisposing genetic defect in multiple endocrine neoplasia type 1 has been assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1 gene have resulted in the isolation of the phosph olipase C beta 3 gene from the actual region. PLCB3 plays an important role in signal transduction and, moreover, shows loss of expression i n some endocrine tumors, in accordance with a putative tumor suppresso r gene function, and thus appears to be an excellent candidate for-MEN 1. We have therefore undertaken screening for constitutional mutations in individuals from MEN1 families. Several sequence alterations have been discovered, none of them however fulfilling the criteria for a di sease-related mutation. We can now exclude PLCB3 from candidacy as the MEN1 gene.