研究人员在MED23基因中发现了一种突变，这种突变与遗传性智力障碍有关。 这些发现因而披露了以某单一基因的相对不明显的破坏作为开始并导致认知缺陷的一连串的事件。
所谓的“错义突变”是指某单一的核苷酸发生转变而产生出一种不同的氨基酸，这种突变可在没有使中介体复合物功能完全停止的情况下影响该中介体复合物的活性。
Satoru Hashinoto及其在法国的同事如今报告说，在MED23 基因中的一个错义突变（该基因编码的是中介体复合物中的某个亚基）与某个阿尔及利亚大家族中的遗传性智力障碍之间存在着相关性。 突变的MED23蛋白会影响JUN与FOS基因的调控，而这些基因本身则与神经元的功能有关。 JUN与FOS基因属于“即刻早期基因”，它们在对某种刺激做出反应的早期扮演着某种作用。
文章的作者提出，在具有这些突变的患者中所观察到的智力障碍可能是（至少部分是）在发育时即刻早期基因表达的精微调节受到损害的结果。
生物探索推荐英文论文摘要：
MED23 Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene ExpressionABSTRACT
MED23 is a subunit of the Mediator complex, a key regulator of protein-coding gene expression. Here, we report a missense mutation (p. R617Q) in MED23 that cosegregates with nonsyndromic autosomal recessive intellectual disability. This mutation specifically impaired the response of JUN and FOS immediate early genes (IEGs) to serum mitogens by altering the interaction between enhancer-bound transcription factors (TCF4 and ELK1, respectively) and Mediator. Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurological disorders linked to mutations in other Mediator subunits or proteins interacting with MED. These findings highlight the crucial role of Mediator in brain development and functioning and suggest that altered IEG expression might be a common molecular hallmark of cognitive deficit.
