Mediator (MED) is a key regulator of protein-coding gene expression, and mutations in MED subunits are associated with a broad spectrum of diseases. Because mutations in MED17 result in autosomal recessive disorders, including microcephaly, intellectual disability, epilepsy, and ataxia, which are barely reported, with only three case reports to date, genotype–phenotype association should be elucidated. Here, we investigated the impact of MED17 mutations on cellular responses and found increased unfolded protein responses (UPRs) in fibroblasts derived from Japanese patients with MED17 mutations. The expression of the UPR genes CHOP and ATF4 was upregulated, and the phosphorylation of eIF2a was basally increased in patients’ cells. Based on our findings, we propose that increased UPRs caused by MED17 mutations might contribute to the clinical phenotype.

介质 (MED) 是蛋白质编码基因表达的关键调节因子，MED 亚基的突变与广泛的疾病有关。由于MED17突变导致常染色体隐性遗传疾病，包括小头畸形、智力残疾、癫痫和共济失调，这些疾病几乎没有报道，迄今为止只有三例病例报告，因此应该阐明基因型-表型关联。在这里，我们研究了MED17突变对细胞反应的影响，并发现源自日本MED17突变患者的成纤维细胞中未折叠蛋白反应 (UPR) 增加。UPR基因CHOP和ATF4的表达上调，并且 eIF2a 的磷酸化在患者细胞中基本增加。根据我们的研究结果，我们提出由MED17突变引起的 UPR 增加可能有助于临床表型。