Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreatic islets and anterior pituitary, which may occur in 95%, >40% and >30% of patients, respectively. Parathyroid tumours, leading to hypercalcaemia, are the first manifestation of MEN1 in >85% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas are more common in patients above the age of 40 years, whilst insulinomas occur more frequently in patients below the age of 40 years. The MEN1 gene, which is located on chromosome 11q13, has been cloned and mutations identified. The human MEN1 gene consists of 10 exons that span >9Kb of genomic DNA and encodes a 610 amino-acid protein, referred to as MENIN. The mutations, which have been identified in MEN1 patients, are scattered widely throughout the 1.83Kb coding region and reveal a great diversity with nonsense, missense, splice site and frameshift deletional and insertional mutations. Combined mutational and clinical studies in >50 unrelated MEN1 families that contained >200 MEN1 mutant gene carriers have helped to define the age-related penetrances of MEN1 as 7%, 52%, 87%, 98%, 99% and 100%, at 10, 20, 30, 40, 50 and 60 years of age, respectively. These clinical and molecular genetic results have helped to define the screening and counselling approaches for MEN1, and thereby improve the management of patients with MEN1. For example, the use of mutational analysis, which is now available, has facilitated the identification of individuals at risk for this endocrine disorder and the development of improved strategies for the earlier detection of MEN1 tumours is likely to reduce morbidity and mortality in these patients.