title: Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism.
abstract: We studied the MEN1 gene in a kindred where three patients (the proposita and two of her sons) were affected with hyperparathyroidism. By polymerase chain reaction (PCR)-based direct sequencing of 10 exons of MEN1, a novel germline mutation was identified in the proposita. This mutation, a T-to-A transition at codon 184 in exon 3, predicts an amino acid change from valine to glutamine (V184E). PCR-single-strand conformational polymorphism (PCR-SSCP) analysis of exon 3 followed by sequencing showed the same mutation in the two sons, and in two clinically normal granddaughters of an affected son. Since the T-to-A substitution segregated with the disorder in the kindred except for the granddaughters and it was not detected in 100 alleles from 50 normal individuals, the change observed in MEN1 is not a polymorphism, but causes familial hyperparathyroidism. Thus the two grandchildren with the mutation were diagnosed as presymptomatic carriers.
authors.affiliation: Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. minoru1@hsp.md.shinshu-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Fujimori
authors.forename: S
authors.initials: S
authors.lastname: Shirahama
authors.forename: A
authors.initials: A
authors.lastname: Sakurai
authors.forename: K
authors.initials: K
authors.lastname: Hashizume
authors.forename: Y
authors.initials: Y
authors.lastname: Hama
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Shingu
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: J
authors.initials: J
authors.lastname: Amano
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018095:Germ-Line Mutation; D005973:Glutamine; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D014633:Valine
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D005973:Glutamine; D014633:Valine