PMID- 24522746 OWN - NLM STAT- MEDLINE DCOM- 20150207 LR - 20211021 IS - 1573-7292 (Electronic) IS - 1389-9600 (Linking) VI - 13 IP - 2 DP - 2014 Jun TI - Deletion of exons 1-3 of the MEN1 gene in a large Italian family causes the loss of menin expression. PG - 273-80 LID - 10.1007/s10689-014-9702-y [doi] AB - Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to inactivating mutations of the MEN1 gene (chromosome 11q13). MEN1 mutations are mainly represented by nonsense, deletions/insertions, splice site or missense mutations that can be detected by direct sequencing of genomic DNA. However, MEN1 patients with large heterozygous deletions may escape classical genetic screening and may be misidentified as phenocopies, thereby hindering proper clinical surveillance. We employed a real-time polymerase chain reaction application, the TaqMan copy number variation assay, to evaluate a family in which we failed to identify an MEN1 mutation by direct sequencing, despite a clear clinical diagnosis of MEN1 syndrome. Using the TaqMan copy number variation assay we identified a large deletion of the MEN1 gene involving exons 1 and 2, in three affected family members, but not in the other nine family members that were to date clinically unaffected. The same genetic alteration was not found in a group of ten unaffected subjects, without family history of endocrine tumors. The MEN1 deletion was further confirmed by multiplex ligation-dependent probe amplification, which showed the deletion extended from exon 1 to exon 3. This new approach allowed us to correctly genetically diagnose three clinical MEN1 patients that were previously considered as MEN1 phenocopies. More importantly, we excluded the presence of genetic alterations in the unaffected family members. These results underline the importance of using a variety of available biotechnology approaches when pursuing a genetic diagnosis in a clinically suggestive setting of inherited endocrine cancer. FAU - Zatelli, Maria Chiara AU - Zatelli MC AD - Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy, ztlmch@unife.it. FAU - Tagliati, Federico AU - Tagliati F FAU - Di Ruvo, Mauro AU - Di Ruvo M FAU - Castermans, Emilie AU - Castermans E FAU - Cavazzini, Luigi AU - Cavazzini L FAU - Daly, Adrian F AU - Daly AF FAU - Ambrosio, Maria Rosaria AU - Ambrosio MR FAU - Beckers, Albert AU - Beckers A FAU - degli Uberti, Ettore AU - degli Uberti E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Fam Cancer JT - Familial cancer JID - 100898211 RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) SB - IM MH - Adolescent MH - Adult MH - Aged MH - *Base Sequence MH - Exons MH - Female MH - Genetic Carrier Screening/*methods MH - Humans MH - Italy MH - Male MH - Middle Aged MH - Multiple Endocrine Neoplasia Type 1/chemistry/*genetics MH - Multiplex Polymerase Chain Reaction MH - Pedigree MH - Proto-Oncogene Proteins/analysis/*genetics MH - Real-Time Polymerase Chain Reaction MH - *Sequence Deletion MH - Young Adult EDAT- 2014/02/14 06:00 MHDA- 2015/02/11 06:00 CRDT- 2014/02/14 06:00 PHST- 2014/02/14 06:00 [entrez] PHST- 2014/02/14 06:00 [pubmed] PHST- 2015/02/11 06:00 [medline] AID - 10.1007/s10689-014-9702-y [doi] PST - ppublish SO - Fam Cancer. 2014 Jun;13(2):273-80. doi: 10.1007/s10689-014-9702-y.