COMMON ANCESTRAL MUTATION IN THE MEN1 GENE IS LIKELY RESPONSIBLE FOR THE PROLACTINOMA VARIANT OF MEN1 (MEN1(BURIN)) IN 4 KINDREDS FROM NEWFOUNDLAND

Familiar multiple endocrine neoplasia type 1 (MEN1) is an autosomal do minant disorder with affected individuals developing parathyroid, gast rointestinal (GI) endocrine, and anterior pituitary tumors, Four large kindreds from the Burin peninsula/Fortune Bay area of Newfoundland wi th prominent features of prolactinomas, carcinoids, and parathyroid tu mors (referred to as MEN1(Burin)) have been described, and they show l inkage to 11q13, the same locus as that of MEN1, Haplotype analysis wi th 16 polymorphic markers now reveals that representative affected ind ividuals from all four families share a common haplotype over a 2.5 Mb region. A nonsense mutation in the MEN1 gene has been found to be res ponsible for the disease in the affected members in all four of the ME N1(Burin) families, providing convincing evidence of a common founder. (C) 1998 Wiley-Liss, Inc.(dagger).