title: A new mutation of the MEN1 gene in an italian kindred with multiple endocrine neoplasia type 1.
abstract: OBJECTIVE
  To report a new mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in an Italian kindred.
  
  
  METHODS
  The study included the female proband, aged 50 years, affected by primary hyperparathyroidism, insulinoma and prolactinoma, and ten relatives. Blood samples were obtained for biochemical and genetic analyses. Clinical screening tests included serum glucose, ionized calcium, intact parathyroid hormone, GH, insulin and prolactin. The coding sequence, including nine coding exons and 16 splice sites, was amplified by PCR and directly sequenced.
  
  
  RESULTS
  Two additional cases of primary hyperparathyroidism were identified among the paternal family members. The sequence analysis showed a heterozygous T to C transition at codon 444 in exon 9, resulting in a leucine to proline substitution (L444P) in the patient and in the two paternal family members with primary hyperparathyroidism. The L444P amino acid change was absent in 50 normal subjects. The mutation determined the loss of a BlnI restriction site of the wild-type sequence and the creation of a new restriction EcoRII site. The patient, but not her paternal affected relatives, also had a common heterozygous polymorphism (D418D) in exon 9.
  
  
  CONCLUSIONS
  A new MEN1 mutation (L444P) in exon 9 has been identified; this substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cetani
authors.forename: E
authors.initials: E
authors.lastname: Pardi
authors.forename: L
authors.initials: L
authors.lastname: Cianferotti
authors.forename: E
authors.initials: E
authors.lastname: Vignali
authors.forename: A
authors.initials: A
authors.lastname: Picone
authors.forename: P
authors.initials: P
authors.lastname: Miccoli
authors.forename: A
authors.initials: A
authors.lastname: Pinchera
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
mesh_terms: D016375:Antisense Elements (Genetics); D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011392:Proline / Q000378:metabolism; D011518:Proto-Oncogene Proteins
chemical_list: D016375:Antisense Elements (Genetics); D003062:Codon; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011392:Proline; D007930:Leucine