Multiple endocrine neoplasia type 1 (MEN 1) is a familial syndrome characterized 
by parathyroid, enteropancreatic and pituitary tumors. The gene responsible for 
this syndrome is localized at chromosomal 11q13 region and DNA markers from this 
region cosegregate with the disease. The recent identification of the MEN1 gene, 
encoding for a protein termed menin of 610 amino acids, allowed mutational 
screening to be performed both in affected families and sporadic cases. To date 
many different heterozygous mutations, spreading across all the encoding 
sequence, have been identified in MEN 1 patients with no apparent mutational hot 
spots or genotype-phenotype correlation. To analyze the genetic alterations of 
the MEN1 gene occurring in Italian patients we performed mutational screening by 
Denaturant Gradient Gel Electrophoresis followed by sequencing of exons 2-10 of 
the MEN1 gene in 27 Italian MEN 1 families and in five sporadic cases. We 
identified 17 different heterozygous mutations in 60% of analyzed cases. Twelve 
of these mutations are novel. Two mutations each occurred twice in unrelated 
families but no evidence of genotype-phenotype correlation can be established 
for these families. The extension of genetic diagnosis to asymptomatic family 
members allowed the identification of 10 MEN1 mutant gene carriers, one newly 
described and nine previously detected by linkage analysis with DNA markers from 
the 11q13 region. Our findings add new information to the diversity of mutations 
occurring in the MEN1 gene and confirm that the mutational screening of MEN 1 is 
a useful approach to detect individuals at higher risk of developing MEN 
1-associated tumors.