Endocrine Abstracts (2019) 65 CC4 | DOI: 10.1530/endoabs.65.CC4

Multiple endocrine neoplasia type 1 (MEN1) mosaicism caused by a c.124G>A variant in the MEN1 gene

Rachel Mauchlen1, David Carty1,2, Maria Talla1 & Russell Drummond1,2


1Glasgow Royal Infirmary, Glasgow, UK; 2University of Glasgow, Glasgow, UK


The MEN1 gene is positioned on the long arm of chromosome 11 (11q13) and results in production of the protein menin. MEN1 mutations produce aberrant menin action or production, although the relationship with tumourigenesis is not clear. Mosaicism is extremely rare, a recent report citing two mosaic cases reported by next generation sequencing1. We describe a 43 year old woman with MEN1 mosaicism associated with parathyroid adenoma and probable pancreatic gastrinoma. Our patient initially presented in 2017 with nephrolithiasis alongside biochemistry that confirmed primary hyperparathyroidism (adjusted Calcium 2.96 mmol/l (2.2–2.6 mmol/l) and PTH 15.9 pmol/l (1.6–7.5 pmol/l)) and imaging confirming a right lower pole parathyroid adenoma. Whilst awaiting her parathyroidectomy, in June 2018 she was admitted with a perforated duodenal ulcer within the first part of the duodenum, ascribed to analgesic ibuprofen. She remained hypercalcaemic post adenoma removal and imaging (later confirmed on pathology) denoted a further culprit right paratracheal parathyroid adenoma which was subsequently removed in March 2019. Whilst her calcium remains normal, a second duodenal perforation (D2) requiring surgery prompted consideration of MEN1. DNA was extracted for next generation sequencing which revealed mosaicism with a c.124 G>A variant in the MEN1 gene at a level of approximately 15%. This variant predicts an amino acid substitution p.(Gly42Ser) in menin structure - an amino acid change previously associated with MEN12. This lady has no first degree family history of note and is hence an index case. Gut hormones and pituitary MRI are awaited. Given the paucity of MEN1 mosaicism reported within the literature, any possible putative hypothesis about a more benign natural history, given the presence of the two cell lines and only 15% mosaicism, is tempting but not possible.

References

1. Coppin et al., 2019 Eur J Endocrinol 1;180(2):L1–L3.

2. Itoh et al., 2017 Clin Pediatr Endocrinol 26; 25–28.

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