A de novo MEN1 gene mutation in a 4-year-old boy with hypoglycemia: A case report and functional study.
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PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary disease involving multiple endocrine glands. However, early diagnosis and precise treatment remain challenging. This study aimed to explore the pathogenicity and function of a novel MEN1 gene mutation (c.583G>T, p.E195*) found in a 4-year-old boy presenting with recurrent hypoglycemic episodes. METHODS: Functional assays were conducted, including the construction of a plasmid containing the MEN1 mutation, co-transfection and luciferase reporter gene assays to assess the impact of the MEN1 mutation on JunD-mediated transcription levels. Empty plasmid vector, wild-type (WT), and mutant MEN1 plasmids were transfected, and the proliferation of tumor cells was assessed using the CCK-8 assay. Statistical analysis was performed using one-way ANOVA with Tukey's post hoc test. RESULTS: The patient was diagnosed with MEN1 and insulinoma via clinical, imaging, pathological, and genetic findings. Hypoglycemia resolved after robotic resection. Genetic testing detected a heterozygous mutation (c.583G>T, p.E195*) in the MEN1 gene. This variation is a de novo mutation. Functional experiments in vitro demonstrated that the MEN1 mutation caused a loss of inhibition on transcriptional activity mediated by the transcription factor JunD. This loss promoted tumor cell proliferation, which led to hypoglycemia caused by the insulinoma. CONCLUSIONS: The novel mutation (c.583G>T, p.E195*) in the MEN1 gene was the causative genetic lesion in this MEN1 patient with insulinoma, and its pathogenicity might partially result from the loss of inhibition of JunD-mediated transcriptional activation caused by the MEN1 mutation.