Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a monogenic, dominantly inherited disorder caused by mutations in the MEN1 gene. Unfortunately, the outcome and the patients’ prognosis are unpredictable even among members of one family. It seems clear that other factors influence the individual outcome of the disease. However, it is still unclear what kind of factors (genetic or environmental) would be responsible for the observed differences.

Aim: We have planned a number of connected studies that aim at identifying the direction in which the reasons for the observed differences in MEN1 outcomes should be searched for. The aim of this work is to present the first part of this study, which is based on evaluating the patients’ genetic background, i.e. the variants in the patients’ genomes. This part of our study focuses on classical genetics.

Methods: We performed high-throughput sequencing that encompassed the whole exomes of 16 patients grouped depending on the outcome of their disease. This patient group included first-degree relatives with different outcomes despite a common underlying MEN1 mutation. Because of the very limited number of patients, the analyses were based on pathways rather than single gene variants.

Results: We present the premise, methods, analyses, and initial results of the first part of our planned multi-step study on the reasons for phenotype differences in MEN1 patients.

Perspectives: In addition to basic genetic factors, the next part of the analyses will encompass also epigenetic and environmental factors, which will be evaluated all together in one final analysis.