%0 Figure %A Wang, Chao %A Lin, Longlong %A Xue, Yan %A Wang, Yilin %A Liu, Zhao %A Ou, Zicheng %A Wu, Shengnan %A Lan, Xiaoping %A Zhang, Yuanfeng %A Yuan, Fang %A Luo, Xiaona %A Wang, Chunmei %A Xi, Jiaming %A Sun, Xiaomin %A Chen, Yucai %D 2020 %T Image_2_MED12-Related Disease in a Chinese Girl: Clinical Characteristics and Underlying Mechanism.jpg %U https://frontiersin.figshare.com/articles/figure/Image_2_MED12-Related_Disease_in_a_Chinese_Girl_Clinical_Characteristics_and_Underlying_Mechanism_jpg/11906304 %R 10.3389/fgene.2020.00129.s002 %2 https://frontiersin.figshare.com/ndownloader/files/21834954 %K MED12 %K mutation %K X-chromosome inactivation %K SHH signaling pathway %K craniofacial morphology %K intellectual disability %X

The RNA polymerase II transcription subunit 12 homolog (MED12) is a member of the mediator complex, which plays a critical role in RNA transcription. Mutations in MED12 cause X-linked intellectual disability and other anomalies collectively grouped as MED12-related disorders. While MED12 mutations have been most commonly reported in male patients, we present the case of a 1-year-old girl with clinical characteristics similar to MED12-related disorders. To explore the clinical characteristics of the condition and its possible pathogenesis, we analyzed the patient’s clinical data; genetic testing by whole-exome sequencing revealed a de novo heterozygous mutation (c.1249-1G > C) in MED12. Further cDNA experiments revealed that the patient had an abnormal splicing at the skipping of exon9, which may have produced a truncated protein. qPCR showed decreased MED12 gene expression level in the patient, and an X-chromosome inactivation test confirmed a skewed inactivation of the X-chromosome. The lymphoblast transcription levels of the genes involved in the Gli3-dependent sonic hedgehog (SHH) signaling pathway, namely, CREB5, BMP4, and NEUROG2, were found to be significantly elevated compared with those of her parents and sex- and age-matched controls. Our results support the view that MED12 mutations may dysregulate the SHH signaling pathway, which may have accounted for the aberrant craniofacial morphology of our patient.

%I Frontiers