Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1)

Dideoxyfingerprinting was used to screen for germline and somatic MENI mutations. This method, applied to a panel of germline DNA from 15 probands with multiple endocrine neoplasia type 1 (MEN-1), allowed confident discovery of the MENI gene. Germline MEN1 mutation has been found in 47 out of 50 probands with familial MEN-I. in 7 out of 8 cases with sporadic MEN-1, and in 1 out of 3 cases with atypical sporadic MEN-1, Germline MENI mutation was not found in any of five probands with familial hyperparathyroidism. Somatic MENI mutations were found in 7 out of 33 parathyroid tumours not associated with MEN-1, Allowing for repeating mutations, a total of 47 different germline or somatic MEN1 mutations have been identified. Most predict inactivation of the encoded 'menin' protein, supporting expectations that MENI is a tumour suppressor gene. The 16 observed missense mutations were distributed across the gene. suggesting that many domains are important to its as yet unknown functions.