A germline mutation, 1001delC, of the multiple endocrine neoplasia type 1 (MEN 1) gene in a Japanese family

Multiple endocrine neoplasia type 1 (MEN I) is an autosomal dominant inheri ted disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary, The MEN 1 gene was recently cloned, and germline mutat ions of the gene have been demonstrated in cases of MEN 1, Here, we report a Japanese family with a germline mutation of the MEN 1 gene. The proband ( 44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcino id, and his older sister (50 y.o.) had a history of parathyroidectomy for p rimary hyperparathyrodism at the age of 40. Clinical examination revealed n o evidence of PHP or other MEN 1-related tumors in his son. Direct sequenci ng analysis revealed a heterozygous germline mutation (1001delC) at codon 2 97 in exon 6 of the MEN 1 gene in the proband and his son. Loss of heterozy gosity (LOH) was also found in the resected parathyroid tissue of the proba nd, The deletion of cytosine 1001 observed in this case induces a frame shi ft, which causes the appearance of a stop codon (TAG) at codon 367, This mu tation appears to be associated with tumors of the endocrine tissues in the cases studied.