-Related Disease in a Chinese Girl: Clinical Characteristics and Underlying Mechanism.

The RNA polymerase II transcription subunit 12 homolog () is a member of the mediator complex, which plays a critical role in RNA transcription. Mutations in cause X-linked intellectual disability and other anomalies collectively grouped as -related disorders. While mutations have been most commonly reported in male patients, we present the case of a 1-year-old girl with clinical characteristics similar to 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 heterozygous mutation (c.1249-1G > C) in . 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 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, , and , were found to be significantly elevated compared with those of her parents and sex- and age-matched controls. Our results support the view that mutations may dysregulate the SHH signaling pathway, which may have accounted for the aberrant craniofacial morphology of our patient.