One genotype with a myriad of phenotypes: A family with multiple endocrine neoplasia

Objective. Multiple endocrine neoplasia type 1 (MEN1) is a very rare genetic disorder characterized by an autosomal dominant inheritance. We aim through this case series to delineate the wide spectrum of its clinical features. Methods. In the present study, we report the clinical and genetic findings of four siblings affected by this disorder. DNA was extracted from patients' blood leukocytes using a phenol-chloroform method and assessed for purity with a NanoDrop spectrophotometer. Ten exons of the MEN1 gene were amplified by PCR, verified by gel electrophoresis, and sequenced using Big Dye Terminator chemistry followed by capillary electrophoresis. The sequences were than analyzed with CHROMAS and compared to reference sequences. As for the variant, interpretation and pathogenicity were assessed using Ensembl, ClinVar, dbSNP, gnomAD, Alamut Visual, and VARSOME. Results. We highlight the wide range of phenotypes encompassing primary hyperparathyroidism, macroprolactinoma, lipomas, papillary thyroid carcinoma, ectopic thyroid, multinodular goiter, and bilateral adrenal nodules observed in this family contrasting with the same pathogenic frameshift mutation. We also pinpoint to a second mutation detected in two of the siblings while discussing its pathogenicity. Finally, we provide an overview of the clinical manifestations of MEN1 and its genetic background. Conclusion. This research sets the stage to further investigate the molecular mechanisms underlying the novel nonsense mutation. Additionally, it incites other research to explore the frequency of this mutation in other populations and finally to conduct functional studies.