Fig. 2

RNA studies (A) Sashimi plot visualization of RNA-seq in F1:II-1 (top) and two control individuals (middle and bottom). The NDUFA5 frameshift variant, c.38_39insG, results in two distinct outcomes for this allele: the introduction of a premature termination codon, which predisposes to nonsense-mediated mRNA decay for transcripts retaining exon 2, and the skipping of exon 2, which leads to an in-frame deletion of 15 amino acids. (B) Allelic imbalance for F1:II-1, showing allele balance bias toward the missense variant c.115C>G (p.Pro39Ala) located in exon 3. (C) Transcript cDNA analysis of NDUFA5 in F2:II-1 and two controls. Individual F2:II-1 has an additional NDUFA5 transcript species compared to the control samples. NTC, no template control. (D) Sequence analysis of NDUFA5 cDNA from F2:II-1 shows aberrant splicing due to the c.183G>A variant by skipping of exon 3 (shown are the exon-exon junctions). (E) Sashimi plot visualization of RNA-seq in F3:II-2 (top) and two control individuals (middle and bottom). The NDUFA5 splice variant, c.183G>A, leads to skipping of exon 3 in the majority of reads.