A new double substitution mutation in the MEN1 gene: a limited penetrance and a specific phenotype

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant cancer syndrome that is caused by a germline mutation in the MEN1 gene encoding a tumour-suppressor protein, menin. MEN1 causes a combination of endocrine tumours such as parathyroid adenomas, pituitary adenomas, glucagonomas, gastrinomas, insulinomas, adrenocortical adenomas and nonendocrine tumours. We here present a large MEN1 family where the carriers developed mild hyperparathyroidism, multiple welldifferentiated functionally active neuroendocrine tumours of the pancreas and no pituitary tumour. The causal mutation is a new double substitution in the coding region of exon 2 in the MEN1 gene c.[428T4A; 429C4T], p.Leu143His. This new mutation in the MEN1 gene is clinically relevant leading to a limited penetrance and specific phenotype.

Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer

“…Not all inherited mutations show the same level of cancer penetrance. Several studies have investigated the degree with which germline mutations lead to cancer phenotypes [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Early phylogenetic studies showed that inherited MEN1 mutations are most likely to be associated with tumors of the parathyroid, pancreas, and pituitary gland [ 57 ].…”

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel <i>CDC73</i> mutation

“…Although HPT-JT is a rare tumor syndrome, it cannot be overlooked because parathyroid carcinoma develops more frequently in this syndrome than other selected for MEN1 (12 articles, 30 patients) [12][13][14][15][16] and HPT-JT (9 articles, 35 patients) [17][18][19][20]. Serum calcium levels ranged from 10.8 to 17.5 mg/dL (mean 12.3 mg/dL, median 13.2 mg/dL) at 25-35 years old in MEN1 cases, and 12.0 to 16.8 mg/dL (mean 13.7 mg/dL, median 11.5 mg/dL) in HPT-JT cases (Fig.…”

Standards of Care Intended for Multiple Endocrine Neoplasia Families

“…The causal mutation is a new double missense substitution in the coding region of exon 2 in the MEN1 gene [26].…”