Table 1.
Overview of skin-derived fibroblast cell lines obtained from healthy controls and patients with a genetic diagnosis of PMD.
| System | Sub-system | Pseudonym | Affected gene (M mtDNA) | NCBI reference sequence | Pathogenic variants (S splice site mutation) |
Heteroplasmy levels (if mtDNA variant) |
|---|---|---|---|---|---|---|
| Control | Control | C1-5; C9; C16-18; C20-25 |
/ | |||
| OXPHOS | CI | P2736 P2737 P45 P2937 P33 P30 P2902 P2943 |
NDUFS2 NDUFS1 TMEM126B MT–ND1M MT–ND1M ACAD9 ACAD9 NUBPL |
NM_004550 NM_005006 NM_018480 NC_012920 NC_012920 NM_014049 NM_014049 NM_025152 |
Homozygous c.1336G > A (p.Asp446Asn) c.1057G > C (p.Ala353Pro), c.420+2T > C (S) c.401delA (p.Arg134IIefs∗2), c.635G > T (p.Gly212Val) m.3928G > C (p.Val208Leu) m.3481G > A (p.Glu59Lys) c.976G > C (p.Ala326Thr), c.1552C > T (p.Arg518Cys) c.1687C > G, (p.His563Asp), c.380G > A (p.Arg127Gln) c.693+1G > A (S), c.351G > A (p.Met117Ile) |
85% 50% |
| CIV | P52 P55 |
SURF1 SURF1 |
NM_003172 NM_003172 |
c.312_321delinsAT (p.Pro104_Leu105insTer), c.544_545delinsCA (p.Val182His) c.845_856del (p.Ser282Cysfs∗), c.870insA (p.Lys291Ter) |
||
| CV | P2264 P2911 |
MT-ATP6M ATP5F1D |
NC_012920 NM_001687 |
m.8993T > G (p.Leu156Arg) Homozygous c.245C > T (p.Pro82Leu) |
ND (fibroblasts); >85% in leukocytes and muscle | |
| Combined | P50 P43 P2912 P2909 P34 |
MT-TDM MRPL44 MRPL44 CARS EARS2 |
NC_012920 NM_022915 NM_022915 NM_005548 NM_133451 |
m.7526A > G Homozygous c.467T>G, (p.Leu156Arg) c.481_484delinsTC (p.Thr161Serfs∗2), c.467T>G (p.Leu156Arg) c.123dupC (p.Lys42Glyfs∗5), c.683C>T (p.Pro228Leu) c.286G>A (p.Gln96Lys), c.500G>A (p.Cys167Tyr) |
2–3% |
|
| PDH | P31 P2130 P2940 |
PDHA1 PDHA1 PDHA1 |
NM_000284 NM_000284 NM_000284 |
c.523G > A (p.Ala175Thr), WT c.904C > T (p.Arg302Cys), WT Hemizygous NA (p.Asn164Ser) |
||
PMD: primary mitochondrial disease, OXPHOS: oxidative phosphorylation system, C: Control, P: Patient, CI: Complex I, CIV: Complex IV, CV: Complex V, PDH: Pyruvate Dehydrogenase NDUFS:NADH Ubiquinone Oxidoreductase Core Subunit, TMEM: transmembrane protein, ND: Complex I subunit; ACAD: Acyl-Coenzyme A Dehydrogenase; NUBPL: Nucleotide Binding Protein Like, SURF: Surfeit Locus Protein, ATP5F1D: ATP Synthase F1 Subunit Delta, MT-TD: Mitochondrially Encoded TRNA-Asp (GAU/C), MRPL: Mitochondrial Ribosomal Protein L, CARS: Cysteinyl-TRNA Synthetase, EARS: Glutamyl-TRNA Synthetase; NA: details not available.