title: A new frameshift MEN1 gene mutation associated with familial malignant insulinomas.
abstract: MEN-1 is an autosomal dominant familial cancer syndrome characterized by involvement of parathyroid, enteropancreatic endocrine tissues and the anterior pituitary gland. Malignant insulinomas are rare, and therefore, there are few data regarding their clinical presentation and long-term prognosis. In this report we present a large family with malignant insulinoma and hyperparathyroidism with MEN-1 gene mutation analysis. A large family (three generations) with several members affected were evaluated for clinical and biochemical characteristic of MEN-1 syndrome. Genetic analysis for MEN1 gene was carried out in all family members using PCR amplification of coding regions followed by direct sequencing. In three brothers that presented with hypoglycemia, insulinoma was confirmed and two were malignant according to pathology and surgery report. Two of them had hyperparathyroidism too. Mutation screening revealed the presence of a two nucleotide deletion in the exon 2 (c199_200del2). In the current study, the deletion happens early in the sequence, and obviously results in a non-functional gene product. However, it will be helpful to further examine somatic mutations and other genetic markers for a more precise study of genotype-phenotype correlation.
authors.affiliation: Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, 5th Floor, Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran. shirinhasanir@yahoo.com
authors.forename: Shirin
authors.initials: S
authors.lastname: Hasani-Ranjbar
authors.forename: Mahsa M
authors.initials: MM
authors.lastname: Amoli
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ebrahim-Habibi
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Gozashti
authors.forename: Nahid
authors.initials: N
authors.lastname: Khalili
authors.forename: Forugh A
authors.initials: FA
authors.lastname: Sayyahpour
authors.forename: Jila
authors.initials: J
authors.lastname: Hafeziyeh
authors.forename: Akbar
authors.initials: A
authors.lastname: Soltani
authors.forename: Bagher
authors.initials: B
authors.lastname: Larijani
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D007340:Insulinoma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins