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

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 non-endocrine tumours. We here present a large MEN1 family where the carriers developed mild hyperparathyroidism, multiple well-differentiated 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.[428T>A; 429C>T], p.Leu143His. This new mutation in the MEN1 gene is clinically relevant leading to a limited penetrance and specific phenotype.