Background and objective: Mutations in the MEN 1 gene were recently discovered as the causative genetic defect of the autosomal dominantly inherited multiple endocrine neoplasia type 1. It was the aim of this study to evaluate the spectrum of MEN 1 mutations in our own series of patients in order to obtain a basis for predictive family screening.
Patients and methods: Genomic DNA from peripheral blood of 21 patients with MEN 1, members of 14 non-related MEN 1 families, was examined for MEN 1 germ-line mutations by means of single-strand conformation variant analysis (SSCP) and direct DNA sequencing. In addition, blood from 20 asymptomatic family members of five families was tested for its predictive value.
Results: Eleven different heterozygotic germ-line mutations, among them eight frameshift, two missense and one nonsense mutations, were identified. In four of the 20 asymptomatic members from five MEN 1 families who had been tested after appropriate genetic counselling, the MEN 1 mutation characteristic for the particular family was found. Clinical screening programme in three mutation carriers revealed abnormal findings in all three: one primary hyperparathyroidism, one prolactinoma and one nonfunctioning pancreatic tumour each. The 16 family members without MEN 1 mutation were spared further unnecessary screening investigations.
Conclusion: Although the function of the MEN 1 gene is not yet known, molecular genetic tests provide a basis for genetic counselling, predictive genetic screening and clinical management of MEN 1 families.