Germline mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in a family with primary hyperparathyroidism

Familial primary hyperparathyroidism (FHP) is a rare hereditary disorder ch aracterized by isolated parathyroid tumors without any other lesions relate d to multiple endocrine neoplasia (MEN). primary hyperparathyroidism is usu ally expressed at an early age and is highly penetrated in MEN type 1 (MEN1 ), suggesting that some FHP may be a variant type or early stage of MEN1. T he MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We studi ed a Japanese family with primary hyperparathyroidism which included 4 pati ents. To investigate the possible relationship between primary hyperparathy roidism in this family and the MEN1 gene, we analyzed a proband for a germl ine mutation of the MEN1 gene in this study. We identified a novel heterozy gous mutation (1350de13) at codon 414 in exon 9. Restriction digestion anal ysis revealed the same mutation pattern in his brother with hyperparathyroi dism. These findings suggest that our patients may belong to a valiant type of MEN1.