MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN 1) is a familial syndrome characte rized by parathyroid, enteropancreatic and pituitary tumors. The gene respo nsible for this syndrome is localized at chromosomal 11q13 region and DNA m arkers from this region cosegregate with the disease. The recent identifica tion of the MEN1 gene, encoding for a protein termed menin of 610 amino aci ds. allowed mutational screening to be performed both in affected families and sporadic cases. To date many different heterozygous mutations, spreadin g 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 pati ents we performed mutational screening by Denaturant Gradient Gel Electroph oresis 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 heter ozygous mutations in 60% of analyzed cases. Twelve of these mutations are n ovel. Two mutations each occurred twice in unrelated families but no eviden ce 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 11q 13 region. Our findings add new information to the diversity of mutations o ccurring 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 M EN 1-associated tumors.