Endocrine Abstracts

Familial pituitary adenoma is frequently associated with germinal mutations of several genes, including menin gene. MEN1 syndrome is an autosomic dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors, and pituitary adenomas, due to inactivating mutations of the MenI gene (11q13). MEN1 mutations are scattered within and around the menin open reading frame and are mainly represented by single nucleotide polymorphisms (SNPs), and small deletions/insertions, which can be detected by genomic DNA direct sequencing. However, heterozygous wide deletions in the menin gene cannot be detected by direct sequencing and other techniques have to be employed to characterize the genetic base of some syndromic families. We employed a real-time PCR application, the TaqMan Copy Number Assay, to evaluate a family in which we failed to identify MEN1 SNPs or deletions/insertions by direct sequencing, despite a clear clinical picture of MEN1 syndrome. By directly evaluating the number of genomic copies by quantitative PCR, we identified a wide deletion of the MEN1 gene involving 50% of exon 1 and 100% of exon 2, in three affected family members, but not in the other seven family members, that are, so far, clinically unaffected. We also evaluated the presence of the same genetic alteration in a group of ten unaffected subject, without family history of endocrine tumors, and none of them displayed exon 1 and 2 deletion. Therefore, this new approach allowed us to correctly diagnose three MEN1 patients that were, so far, considered as MEN1 phenocopies. More importantly, we were able to exclude the presence of any MEN1 genetic alteration in the unaffected family members. These results further underline the importance of the new biotechnology approaches in the diagnosis of genetically determined endocrine diseases.