NOVEL V184E MEN1 GERMLINE MUTATION IN A JAPANESE KINDRED WITH FAMILIAL HYPERPARATHYROIDISM

We studied the MEN1 gene in a kindred where three patients (the propos ita and two of her sons) were affected with hyperparathyroidism. By po lymerase chain reaction (PCR)-based direct sequencing of 10 exons of M EN1, a novel germline mutation was identified in the proposita, This m utation, a T-to-A transition at codon 184 in exon 3, predicts an amino acid change from valine to glutamine (V184E), PCR-single-strand confo rmational polymorphism (PCR-SSCP) analysis of exon 3 followed by seque ncing showed the same mutation in the two sons, and in two clinically normal granddaughters of an affected son. Since the T-to-A substitutio n segregated with the disorder in the kindred except for the granddaug hters and it was not detected in 100 alleles from 50 normal individual s, the change observed in MEN1 is not a polymorphism, but causes famil ial hyperparathyroidism, Thus the two grandchildren with the mutation were diagnosed as presymptomatic carriers. (C) 1998 Wiley-Liss, Inc.