GERMLINE MUTATIONS OF THE MEN1 GENE IN JAPANESE KINDRED WITH MULTIPLEENDOCRINE NEOPLASIA TYPE-1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant fa milial cancer syndrome, The responsible gene MEN1 has recently been is olated, and its germline mutations have been identified in affected in dividuals in the United States, Canada and Europe. We screened for MEN 1 mutations by direct nucleotide sequencing of all protein-coding regi ons, and identified five distinct germline mutations in five among six Japanese kindreds with familial MEN1 or familial hyperparathyroidism. The mutations were dispersed across the gene. These findings suggest that, because of the absence of an obvious founder effect, the entire MEN1 gene region should be examined for germline mutations in the prob ands of MEN1 and related syndromes in Japanese families.