A. Morelli et al., GENETIC SCREENING TO IDENTIFY THE GENE CARRIER IN ITALIAN AND GERMAN KINDREDS AFFECTED BY MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 (MEN-1) SYNDROME, Journal of endocrinological investigation, 18(5), 1995, pp. 329-335
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 gastro
enteric 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 I gene
has been mapped by genetic studies to the long arm of human chromosom
e 11, region q12-13. Genetic analysis of families and tumoral deletion
mapping made possible to narrow the men I region to a 5 cM interval o
n chromosome 11q12-13. Thirteen marker complexes (17 DNA probes) were
found to be linked to the men I gene and they span a 14% meiotic recom
bination 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 DN
A markers (10 DNA probes) of the chromosome region where the men I gen
e maps (11q12-13), we identified 10 mutant gene carriers. The predicte
d MEN 1 diagnosis was clinically confirmed for 2 of these identified c
arriers, A predictive accuracy of this genetic test can reach up to 99
.5% when it is possible to exclude meiotic crossing-over between the a
nalyzed DNA markers and the disease locus.