A de novo MEN1 gene mutation in a 4-year-old boy with hypoglycemia: A case report and functional study.

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.