title: Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma.
abstract: Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein'menin' involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease.
  
  
  CONCLUSIONS
  Identification of a novel pathogenic MEN1 deletion mutation.MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology.Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome.
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy , All India Institute of Medical Sciences , New Delhi 110029 , India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Birla
authors.affiliation: Department of Endocrinology and Metabolism , All India Institute of Medical Sciences , New Delhi 110029 , India.
authors.forename: Viveka
authors.initials: V
authors.lastname: P Jyotsna
authors.affiliation: Department of Endocrinology and Metabolism , All India Institute of Medical Sciences , New Delhi 110029 , India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Singla
authors.affiliation: Department of Nuclear Medicine , All India Institute of Medical Sciences , New Delhi 110029 , India.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Tripathi
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy , All India Institute of Medical Sciences , New Delhi 110029 , India.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Sharma