TABLE 3. Common neurodevelopmental sequelae of mutations in nuclear genes.
More than 60 nuclear genes have now been implicated in the pathogenesis of mitochondrial disease. This table lists roles and names of specific nuclear genes that cause major neurodevelopmental manifestations in the pediatric population.
| Leuko-Encephalopathy: | Basal Ganglia Abnormalities: | Ataxia: | Seizures: | Peripheral Neuropathy: | Dystonia: |
|---|---|---|---|---|---|
| 12 (of 38) nuclear-encoded complex I subunits or 5 assembly factors (83) | 12 (of 38) nuclear-encoded complex I subunits or 5 assembly factors (83) | Incorporate heme into complex IV (COX10) (88) | Complex I structural subunits (52) | Coenzyme Q10 deficiency (APTX) (94) | Mitochondrial transporter gene (DDP1) (84) |
| Complex III assembly factor (BCS1L) (85, 86) | Complex II subunits (SDHA) (87) | Coenzyme Q10 biosynthetic pathway enzyme (PDSS2) | Incorporate heme into complex IV (COX10) (88) | mtDNA depletion (POLG1, RRM2B) (51, 102) | |
| Complex IV copper incorporation (SCO1) (89) or matrix formation (ETHE1) (90) | Complex IV assembly factors (SURF1, COX15, or ETHE1) (90-92) | Coenzyme Q10 deficiency (APTX, ADCK3) (93, 94) | Complex V assembly factor (ATP12) (58) | Nucleotide salvage (ECGF1) (109) | |
| Complex V assembly factor (ATP12) (58) | Complex IV mRNA processing protein (LRPPRC) (95) | mtDNA deletions (POLG1, TWINKLE) (96) | Coenzyme Q10 biosynthetic pathway enzymes (PDSS2, COQ2) (98, 99) | Impaired metalloprotease activity (SPG7) (97) | |
| Coenzyme Q10 biosynthetic pathway enzymes (PDSS2, COQ2) (98, 99) | Complex V assembly factor (ATP12) (100) | Abnormal iron export (ABC7) (101) | mtDNA depletion (POLG1, RRM2B) (102) | ||
| Multiple RC deficiency due to abnormal mtDNA translation (TSFM, TUFM, EFG1, DARS2) (103) | Multiple RC enzyme deficiency (EFG1, DARS2) (104, 105) | Abnormal iron storage (FXN) (106) | |||
| Pyruvate dehydrogenase enzyme components (PDHA1 or other complex components) (61) | Pyruvate dehydrogenase enzyme components (PDHA1 or other complex components) (107) | ||||
| mtDNA depletion due to abnormal mtDNA replication (POLG1) (51) and/or nucleotide salvage (DGUOK, MPV17, ECGF1) (108-110) |