Fig. 4

Analysis of patients carrying mitochondrial DNA (mtDNA) deletions. (a) Detection of single deletion from single-end sequencing. Gel electrophoresis with Patient P1 harboring a heteroplasmic single deletion of approximately 5 kb detected by long-range polymerase chain reaction (PCR) analysis in muscle and uroepithelial cells. Circos graphical representations with the common deletion (m.8470_13447del) in muscle (left) and urine (right) samples with respectively 56% and 3.5% of mutant loads. (b) Detection of single deletion from paired-end sequencing. Gel electrophoresis with patient P2 carrying a heteroplasmic single deletion of about 4 kb in muscle. Circos graphical representation showing the presence of a 3826-bp deletion (m.8559_12385del) at 77% mutant load. (c) Detection of multiple deletions from single-end sequencing. Gel electrophoresis with patient P3 harboring two pathogenic variants in DGUOK and patient P4 carrying two likely pathogenic variants in POLG. Circos graphical representations of patients P3 (left) and P4 (right) with the number of deletions (red arcs) identified by eKLIPse. (d) Detection of multiple deletions from paired-end sequencing. mtDNA long-range PCR gel electrophoresis with patient P5 carrying two pathogenic variants in SLC25A4 associated with multiple deletions. Circos graphical representation of patient P5 showing multiple deletions (red arcs).