Two females with distinct de novo missense pathogenic variants in MED12 and vastly differing phenotypes

Abstract

The MED12 gene has an important role in neuronal gene silencing (Ding et al., 2008;Graham Jr & Schwartz, 2013) and has been associated with four distinct X-linked intellectual disability (ID) conditions: FG syndrome, Lujan syndrome, Ohdo syndrome, and nonspecific ID. Its gene product is part of the large Mediator complex comprised of 31 subunits arranged in four modules that interacts with RNA polymerase II and plays a critical role in regulating transcription (Yin & Wang, 2014). The complex is involved in cell growth, development, and differentiation through epigenetic regulation, transcriptional elongation, termination, mRNA processing, noncoding RNA activation, and super enhancer formation (Graham Jr & Schwartz, 2013).