Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family

Sandra Mastroianno, Massimo Torlontano, Alfredo Scillitani, Leonardo D'Aloiso, Antonella Verrienti, Nazario Bonfitto, Antonio De Bonis, Leonardo D'Agruma, Lucia Anna Muscarella, Vito Guarnieri, Franca Dicembrino, Marianna Maranghi, Cosimo Durante, Sebastiano Filetti

Research output: Contribution to journalArticlepeer-review


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 germlinemutationswere found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both themutations. 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.

Original languageEnglish
Pages (from-to)481-485
Number of pages5
Issue number3
Publication statusPublished - Dec 2011


  • Medullary thyroid cancer
  • MEN1
  • MEN2
  • Primary hyperparathyroidism

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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