To describe the coexistence of mutations of both the multiple endocrine 
neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and 
evaluate if it could be associated with more aggressive clinical manifestations 
of the two syndromes. Blood samples were obtained for genetic and biochemical 
analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding 
regions, including the exon-intron boundaries, were amplified by PCR and 
directly sequenced. We identified two germline mutations in the proband: the 
first one, K666M, located at the exon 11 of RET proto-oncogene and the second 
one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of 
IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, 
caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter 
protein. The same proband's germline mutations were found in 16 relatives out of 
21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both the 
mutations. This is the second report in literature of coexistence in the same 
family of germline mutations of both RET proto-oncogene and MEN1 gene. The 
simultaneous presence of the two mutations was not apparently associated with 
more aggressive diseases, since at last follow-up all patients appeared to be 
disease-free or well compensated by medical therapy; finally, no one exhibited 
metastatic diseases.