SUN-909 A Unique Presentation of Multiple Endocrine Neoplasia (MEN) Type 1 Mosaicism Caused by a Novel c.124G>A Variant in the MEN1 Gene

Abstract

The MEN1 gene is positioned on the long arm of chromosome 11 (11q13) and results in the production of menin. A classical tumour suppressor gene; the spectrum of reported germline MEN1 mutations occur throughout the gene with no strong genotype/phenotype relationship. Mosaicism is extremely rare, a recent report citing only 2 mosaic cases by next generation sequencing1. We describe a 43-year-old female with MEN1 mosaicism associated with parathyroid adenoma and probable gastrinoma.Our patient initially presented with nephrolithiasis and nephrocalcinosis alongside biochemistry of primary hyperparathyroidism. Imaging confirmed a right lower pole parathyroid adenoma and the lesion was removed, pathology confirming the diagnosis (July 2018). Post operatively she remained hypercalcaemic. Repeat imaging suggested a further right sided culprit lesion.One year previously (August 2017) she was admitted with a perforated duodenal ulcer within the first part of the duodenum (D1), ascribed to ibuprofen use, requiring surgical repair. Whilst awaiting repeat parathyroid surgery she represented with a further duodenal ulcer and perforation (February 2019) this time in the second part of the duodenum(D2). A second parathyroidectomy was performed and genetic investigations were instigated, given the presence of classical MEN1 phenotype. Again, pathology was consistent with a parathyroid adenoma (March 2019).DNA was extracted for next generation sequencing which revealed mosaicism with a c.124 G>A variant detected in the MEN1 gene at a level of approximately 15%.Further investigations have shown normal serum prolactin and pituitary and pancreatic MRI imaging. With no other family members testing positive (parents and 2/3 children) this mutation appears to be a de novo index case. Adjusted Calcium is normal 2.53 mmol/L (2.2-2.6 mmol/L) but serum Chromogranin A is elevated (2620 µg/L (ref range <95 µg/L)).The c.124 G>A variant predicts an amino acid substitution p.(Gly42Ser) in menin structure, an amino acid change previously associated with MEN12. Given the paucity of MEN1 mosaicism reported within the literature with the presence of the two cell lines and only 15% mosaicism close monitoring will be crucial to determine the genotype/phenotype relationship in our patient. 1 Choppin et al 2019 Eur J Endocrinol 1; 180(2):L1-L3 2 Itoh et al 2017 Clin Pediatr Endocrinol 26;25-28