Novel Synonymous and Deep Intronic Variants Causing Primary and Secondary Pyruvate Dehydrogenase Complex Deficiency

Figure 3

RNA analyses of PDHX in RNA from blood. (a) PCR products of PDHX cDNA generated from RNA from patient 3 (P3), her affected sister (P4), parents, and control (C) blood, showing longer products than wild type in the patients. (b) Schematic picture of variants identified in P3 and P4 PDHX on DNA level and the resulting aberrantly spliced mRNAs. (c) Box plot showing total gene expression of PDHX in blood in P3 and P4 and their parents compared to the control group of 135 healthy individuals. (d) Sashimi plot of RNAseq data from blood from P3, her parents, and the control group consisting of the median number of reads in 10 healthy controls. RNA coverage is given on the axis, and a number of split reads spanning introns are indicated on the exon junction lines. Bottom graph depicts MANE Select transcript (ENST00000227868.8, NM_003477.3) with reference exons 7-10 as black boxes. The dashed box marks the position of the included pseudoexon from intron 9. No wild-type splice junctions from exons 8 to 9 are visible in P3.

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