Endocrine Abstracts

Background: Multiple endocrine neoplasia type 1 (MEN1) (OMIM 131100) is an autosomal dominant disorder associated with a high risk of developing parathyroid hyperplasia (90%), digestive neuroendocrine tumors (30–70%) and pituitary adenomas (30-40%). Prevalence of MEN1 is 2-10/100.000, there are no differences between men and women and usually, it is diagnosed before 40 years old. It is related to different mutations of the MEN1 tumour-suppressor gene (OMIM: 613733) which is located on chromosome 11 (11q13), has 10 exons and encodes a nuclear protein of 610 amino acids. More than 100 genetic variants have been identified and most of them are located in coding regions.

Method: We retrospectively analyzed fifteen cases in the last five years. We selected all the patients with two or more tumors associated with MEN1 consequently they were evaluated by a multidisciplinary team who decided to do MEN1 genetic diagnostic test. After a complete clinical-biochemical assessment of each patient, samples were taken. MEN1 gene was amplified by PCR and sequenced. This study does not allow to detect large deletions. Pathological variants were confirmed by Sanger sequencing.

Results: The average age of patients is 42±14.52 years, 80% are women and 20% men. Also, 90% of the patients present primary hyperparathyroidism. A genetic test revealed the presence of heterozygous variants within the coding region in two women (13%). These variants are missense mutation with a changed aminoacid and they have been described as pathogenic and moreover associated with MEN. No other variants were detected in the other patients. However, large deletions in MEN1 were not analyzed.

Conclusions: In patients with suspected MEN1, the gene should be studied by sequencing it and If no mutations are detected the laboratory should look for large deletions through Multiplex ligation-dependent probe amplification (MLPA) (1–3% cases). There are other genes whose mutations give rise to syndromes similar to MEN1. For this reason, it is important to evaluate other genes like CDKN1B or AIP especially when we do not find any mutation in the MEN1 gene. An interesting option could be to use genetic testing with comprehensive gene panels because this will allow us to detect more genes alterations and different pathologies.