title: Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism.
abstract: BACKGROUND
  Familial isolated hyperparathyroidism (FIHP) is a hereditary disorder characterised by uni- or multiglandular parathyroid disease. A subset of families are likely to be genetic variants of other familial tumour syndromes in which PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT).
  
  
  OBJECTIVE
  To investigate seven families diagnosed with FIHP, each with two to eight affected family members, to clarify the underlying genetic mechanism.
  
  
  METHODS
  The entire MEN1 gene was sequenced for germline mutations and, in addition, tumour specimens were analysed in comparative genomic hybridisation and loss of heterozygosity studies.
  
  
  RESULTS
  Two families exhibited MEN1 mutations, L112V and 1658delG, which were associated with loss of the wild-type 11q13 alleles in all tumours analysed. In the remaining five families, no MEN1 mutation was identified.
  
  
  CONCLUSIONS
  These results support the involvement of the MEN1 tumour suppressor gene in the pathogenesis of some of the FIHP kindreds. However, loss on chromosome 11 was seen in all tumours exhibiting somatic deletions, although in two families the tumour deletions involved 11q distal to MEN1. We conclude that the altered MEN1 gene function is of importance in the development of FIHP.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. Andrea.Villablanca@cmm.ki.se
authors.forename: Andrea
authors.initials: A
authors.lastname: Villablanca
authors.forename: Wassif S
authors.initials: WS
authors.lastname: Wassif
authors.forename: Thomas
authors.initials: T
authors.lastname: Smith
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
authors.forename: Outi
authors.initials: O
authors.lastname: Vierimaa
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Trisha
authors.initials: T
authors.lastname: Dwight
authors.forename: Lars
authors.initials: L
authors.lastname: Forsberg
authors.forename: Quan
authors.initials: Q
authors.lastname: Du
authors.forename: Diana
authors.initials: D
authors.lastname: Learoyd
authors.forename: Keston
authors.initials: K
authors.lastname: Jones
authors.forename: Steve
authors.initials: S
authors.lastname: Stranks
authors.forename: Claes
authors.initials: C
authors.lastname: Juhlin
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Tobias
authors.initials: T
authors.lastname: Carling
authors.forename: Bruce
authors.initials: B
authors.lastname: Robinson
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000328:Adult; D000368:Aged; D002880:Chromosomes, Human, Pair 11; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D005838:Genotype; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D017422:Sequence Analysis, DNA