Genetic screening to identify the gene carrier in Italian and German kindreds affected by multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominantly inherited disorder characterized by parathyroid hyperplasia, anterior pituitary adenomas and neoplasms of the endocrine cells of the gastroenteric tract. It has been established that also other tissues exhibit excessive proliferation associated to the MEN 1 syndrome: carcinoids (bronchial and intestinal), lipomas (visceral and cutaneous), thyroid adenomas and goiter, and adrenal gland cortex adenomas. The men 1 gene has been mapped by genetic studies to the long arm of human chromosome 11, region q12-13. Genetic analysis of families and tumoral deletion mapping made possible to narrow the men 1 region to a 5 cM interval on chromosome 11q12-13. Thirteen marker complexes (17 DNA probes) were found to be linked to the men 1 gene and they span a 14% meiotic recombination with the men 1 locus in the middle. We report a genetic study on 103 subjects from 7 collected MEN 1-kindreds, six Italian and one German, including 30 affected individuals. By linkage analysis to 9 DNA markers (10 DNA probes) of the chromosome region where the men 1 gene maps (11q12-13), we identified 10 mutant gene carriers. The predicted MEN 1 diagnosis was clinically confirmed for 2 of these identified carriers. A predictive accuracy of this genetic test can reach up to 99.5% when it is possible to exclude meiotic crossing-over between the analyzed DNA markers and the disease locus.