A new mutation of the MEN1 gene in an Italian kindred with multiple endocrine neoplasia type 1

Objective: To report a new mutation of the multiple endocrine neoplasia typ e 1 (MEN1) gene in an Italian kindred. Design: The study included the female proband, aged 50 years, affected by p rimary 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 parathyroi d hormone, GH, insulin and prolactin. The coding sequence, including nine c oding exons and 16 splice sites, was amplified by PCR and directly sequence d. Results: Two additional cases of primary hyperparathyroidism were identifie d among the paternal family members, The sequence analysis showed a heteroz ygous T to C transition at codon 444 in exon 9, resulting in a leucine to p roline substitution (L444P) in the patient and in the two paternal family m embers with primary hyperparathyroidism. The L444P amino acid change was ab sent in 50 normal subjects, The mutation determined the loss of a BlnI rest riction site of the wild-type sequence and the creation of a new restrictio n EcoRII site. The patient, but not her paternal affected relatives, also h ad a common heterozygous polymorphism (D418D) in exon 9. Conclusions: A new MEN1 mutation (L444P) in exon 9 has been identified; thi s substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.