Cancer genetics · 2026
A de novo MEN1 gene mutation in a 4-year-old boy with hypoglycemia: A case report and functional study.
СтатьяКлинический случайНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Jia, Wang Xin-Jing, Zhang Li-Dan, Yu Yi, Xiao Yuan, Xu Chun-Di, Ye Lei, Wang Xin-Qiong, Ma Xiao-Yu, Li Chuan-Yin, Lu Wen-Li
Аннотация
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.
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.