title: Novel MEN 1 gene findings in rare sporadic insulinoma--a case control study.
abstract: BACKGROUND
  Insulinomas, which are rare tumors causing hyperinsulinemic hypoglycemia are usually sporadic but may also occur in association with multiple endocrine neoplasia type 1 (MEN-1) syndrome an autosomal dominant disorder caused by MEN1 gene mutations. MEN1 encodes a nuclear protein Menin, a tumor suppressor which acts as an adapter and interacts with partner proteins involved in crucial activities like transcriptional regulation, cell division, proliferation and genome stability. This study reports on clinical findings and mutation screening in sporadic insulinoma patients.
  
  
  METHODS
  Seventeen patients diagnosed with insulinoma were recruited along with 30 healthy volunteers who acted as controls for the present study. The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain. Detailed clinical and family history was collected from all the participants along with 5 ml of blood sample after taking informed consent. Genomic DNA isolated from blood was subjected to MEN1 gene amplification followed by direct sequencing. Nucleotide sequences obtained were compared with published MEN1 cDNA sequences. Prediction of functional effects of novel changes was done using various bioinformatics algorithms.
  
  
  RESULTS
  Molecular analysis revealed presence of three novel exonic mutations (M561K, Q192K and Q261Q), two novel intronic variations c.445-44G → A and c.913-42G → C in introns two and six respectively and three reported exon SNPs; H433H (rs540012), D418D (rs2071313), A541T (rs2959656) and one intronic SNP (rs669976).
  
  
  CONCLUSIONS
  The study identified presence of novel pathogenic MEN1 mutations in sporadic cases of insulinoma. The new mutations identified were in regions involved in defective binding of menin to proteins implicated in genetic and epigenetic mechanisms. The outcome of the study extends the growing list of MEN1 pathogenic mutations even in sporadic cases providing consequential insight into phenotypic heterogeneity and in the expression of individual mutations.
authors: Department of Endocrinology and metabolism, All India Institute of Medical Sciences, Room No. 305, Third Floor, Biotechnology Building, New Delhi, India. vivekapjyotsna@gmail.com.
authors: Viveka P
authors: VP
authors: Jyotsna
authors: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. malikekta86@gmail.com.
authors: Ekta
authors: E
authors: Malik
authors: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. sbirla84@gmail.com.
authors: Shweta
authors: S
authors: Birla
authors: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. arundhatisharma1@gmail.com.
authors: Arundhati
authors: A
authors: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007340:Insulinoma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins