Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual phenotype of striatal involvement.

RNA polymerase III is essential for the transcription of non-coding RNAs, including tRNAs. Mutations in the genes encoding its largest subunits are known to cause hypomyelinating leukodystrophies (HLD7) with pathogenetic mechanisms hypothesised to involve impaired availability of tRNAs. We have identified a founder mutation in the POLR3A gene that leads to aberrant splicing, a premature termination codon and partial deficiency of the canonical full-length transcript. Our clinical and imaging data showed no evidence of the previously reported white matter or cerebellar involvement; instead the affected brain structures included the striatum and red nuclei with the ensuing clinical manifestations. Our transcriptome-wide investigations revealed an overall decrease in the levels of Pol III-transcribed tRNAs and an imbalance in the levels of regulatory ncRNAs such as small nuclear and nucleolar RNAs (snRNAs and snoRNAs). In addition, the Pol III mutation was found to exert complex downstream effects on the Pol II transcriptome, affecting the general regulation of RNA metabolism.

Quantitative assessment of pterygomasseteric hypertrophy.

The aim of this study was to quantify the pterygomasseteric hypertrophy in a clinical case with significant facial asymmetry and temporomandibular joint dysfunction. Magnetic resonance imaging (MRI) technique was used to measure the surface areas of affected and contralateral pterygomasseteric muscle groups on six coronal scans. The results suggest that MRI is a very effective method for quantification of muscular hypertrophy and better explanation of associated clinical findings, therefore motivating the need to preserve or restore the bilateral masticatory function.