8184 A Case With Primary Hyperparathyroidism Caries A New Variant Of Uncertain Significance (VUS) Of The Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

Abstract Disclosure: E. Caliskan Guzelce: None. E. Fieg: None. C. Pallias: None. Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder caused by mutations in the MEN1 tumor suppressor gene. MEN1 syndrome is classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary, and pancreatic islet cells. However, the clinical spectrum of this disorder has been expanded: carcinoid tumors,adrenal adenomas and lipomas are more common than in the general population.We report a case whose personal and family history is highly suggestive of and consistent with a monogenic disorder such as MEN1, also found to be a carrier of a new variant of uncertain significance (VUS) of the MEN1 gene. A study performed with the French Universal Mutation Database (UMD) for the MEN1 gene showed that one-third of the missense MEN1 variants were VUSs, mainly due to the lack of clinical and segregation data. Therefore, it is very important to identify and report the subjects with VUS of the MEN1 gene. Case report: 68-year-old female with a past medical history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, CKD stage 4, and nephrolithiasis, GERD who presented with chief complaints of nausea and upper abdominal/epigastric pain and dark stools and found to have moderate hypercalcemia c/w primary hyperparathyroidism, several pancreatic cystic lesions most likely branch duct intraductal papillary mucinous neoplasms, and multinodular goiter and adrenal adenoma. Family history significant for recurrent hyperparathyroidism and nephrolithiasis; her daughter and brother had nephrolithiasis; her daughter has undergone parathyroidectomy twice. The patient's mother died at a young age because of gastric ulcer-related complications. Hyperparathyroidism-related genes were analyzed; AP2S1, CASR, CDC73, CDKN1B, GNA11, RET, MEN1, and only a Variant of Uncertain Significance, c.247_249dup (p.Leu83dup), was identified in MEN1 gene. The patient’s daughter and granddaughter are found to have the same mutation. Conclusion: This variant, c.247_249dup, results in the insertion of 1 amino acid(s) of the MEN1 protein (p. Leu83dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). The literature has not reported this variant in individuals affected with MEN1-related conditions. Presentation: 6/3/2024