title: Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism.
abstract: OBJECTIVE
  Primary hyperparathyroidism (PHPT) can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein "menin." We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT.
  
  
  METHODS
  Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent.
  
  
  RESULTS
  Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients.
  
  
  CONCLUSIONS
  This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Birla
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: E
authors.initials: E
authors.lastname: Malik
authors.affiliation: Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.
authors.forename: V P
authors.initials: VP
authors.lastname: Jyotsna
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy, AIIMS, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
keywords: Multiple endocrine neoplasia type 1 gene; mutations; primary hyperparathyroidism