Introduction
Mitochondrial genetics
Gene | Inheritance | Onset | Common clinical manifestation/syndrome | |
---|---|---|---|---|
OXPHOS system | ||||
Complex I | ||||
Structural subunit |
NDUFA2, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFB3, NDUFB9, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8
| AR | Infancy | Leigh syndrome, encephalopathy, cardiomyopathy, epilepsy, lactic acidosis |
NDUFA1, NDUFB11
| X-linked | Leigh syndrome, microphthalmia with linear skin defects | ||
Assembly factor |
ACAD9, NDUFAF1, NDUFAF2, NDUFAF4, NDUFAF5, NDUFAF6, FOXRED1
| AR | Leigh syndrome, encephalopathy, cardiomyopathy | |
Complex II | ||||
Structural subunit |
SDHA-D
| AR | Infancy, childhood | Leigh syndrome, dilated cardiomyopathy |
AD | Childhood, adulthood | Hereditary paraganglioma, pheochromocytoma | ||
Assembly factor |
SDHAF1
| AR | Infancy | Spastic quadriplegia, leukodystrophy |
SDHAF2
| AD | Adulthood | Hereditary paraganglioma, pheochromocytoma | |
Complex III | ||||
Structural subunit |
UQCRB
| AR | Childhood | Hypoglycaemia, lactic acidosis |
UQCRQ
| AR | Childhood | Extrapyramidal signs, ataxia, psychomotor retardation | |
Assembly factor |
BCS1L
| AR | Infancy | Growth retardation, aminoaciduria, cholestasis, iron overload, and early death (GRACILE) |
TTC19
| AR | Childhood, adulthood | Encephalomyopathy, ataxia | |
Complex IV | ||||
Structural subunit |
COX6B1, NDUFA4
| AR | Infancy, childhood | Encephalomyopathy, Leigh-like syndrome |
COX4I2
| AR | Infancy, childhood | Exocrine pancreatic insufficiency, dyserythropoetic anaemia (similar to Pearson syndrome), calvarial hyperostosis | |
Assembly factor |
SURF1, SCO1-2, COX10, COX15, LRPPRC, COA5, PET100
| AR | Infancy | Leigh syndrome, French-Canadian Leigh syndrome, hypertrophic cardiomyopathy, encephalomyopathy |
Complex V | ||||
Structural subunit |
ATP5E
| AR | Infancy | Encephalopathy, dysmorphic features, hypertrophic cardiomyopathy, lactic acidosis |
Assembly factor |
ATPAF2, TMEM70
| AR | ||
Co-enzyme Q10 biosynthesis | ||||
Co-enzyme Q10 deficiency |
COQ2, COQ4, COQ6, PDSS2
| AR | Infancy, childhood | Encephalomyopathy, nephrotic syndrome, sensori-neural deafness |
ETFDH
| AR | Infancy, childhood, adulthood | Glutaric acidaemia IIC (multiple acyl-CoA dehydrogenase deficiency, MADD), Myopathy | |
ADCK3
| AR | Childhood | Cerebellar ataxia | |
Mitochondrial DNA replication | ||||
MtDNA depletion or multiple deletions |
POLG
| AD | Adulthood | Chronic progressive external ophthalmoplegia (CPEO) |
AR | Infancy, childhood, adulthood | CPEO, Alpers disease, ataxia-neuropathy syndrome, Leigh syndrome, epilepsy (occipital), Parkinsonism | ||
PEO1 (c10orf2) | AD | Adulthood | CPEO | |
AR | Infancy | Inherited Infancy onset of spinocerebellar ataxia (IOSCA), hepatocerebral syndrome | ||
MtDNA multiple deletions |
POLG2
| AD | Adulthood | CPEO |
Nucleotide synthesis and transport (maintenance) | ||||
MtDNA depletion or multiple deletions |
TYMP
| AR | Childhood, adulthood | Mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) |
RRM2B
| AD | Adulthood | CPEO | |
AR | Infancy | Encephalomyopathy, gut dysmotility, Kearns-Sayre syndrome (KSS), proximal renal tubulopathy | ||
SLC25A4 (ANT1) | AD | Adulthood | CPEO | |
AR | Childhood | Hypertrophic cardiomyopathy, lactic acidosis | ||
TK2
| AR | Infancy, childhood, adulthood | Myopathy and respiratory muscle weakness | |
MPV17
| AR | Infancy, childhood, adulthood | Hepatocerebral syndrome, neuropathy and leukoencephalopathy | |
MtDNA depletion |
DGUOK
| AR | Infancy | Hepatocerebral syndrome |
SUCLA2, SUCLG1
| AR | Infancy | Encephalomyopathy, raised methylmalonic acid, hyperkinesia | |
MtDNA multiple deletions |
DNA2
| AD | Adulthood | CPEO |
No change in mtDNA content/unknown |
SLC25A3
| AR | Infancy | Hypertrophic cardiomyopathy, hypotonia |
GFER
| AR | Childhood, adulthood | Congenital cataract, myopathy, cardiomyopathy | |
Mitochondrial translation | ||||
Multiple respiratory chain deficiency | ||||
Ribosomal protein |
MRPS16
| AR | Infancy | Dysmorphism, lactic acidosis, agenesis of corpus callosum |
MRPS22
| AR | Infancy | Cardiomyopathy, tubulopathy, hypotonia | |
Elongation factor |
GFM1, TUFM
| AR | Infancy | Leigh syndrome |
TSFM
| AR | Infancy, childhood | Encephalopathy, hypertrophic cardiomyopathy | |
tRNA modification |
PUS1
| AR | Infancy, childhood | Myopathy, lactic acidosis and sideroblastic anaemia (MLASA) |
MTFMT
| AR | Infancy, childhood | Encephalomyopathy | |
TRIT1
| AR | Childhood | Encephalopathy, myoclonic epilepsy | |
tRNA synthetases |
AARS2
| AR | Infancy | Hypertrophic cardiomyopathy, myopathy |
CARS2
| AR | Childhood | Epileptic encephalopathy, myoclonus | |
DARS2
| AR | Childhood, adulthood | Leukoencephalopathy in brainstem and spinal cord involvement and lactate elevation (LBSL) | |
EARS2
| AR | Infancy, childhood | Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) | |
GARS
| AD | Childhood, adulthood | Charcot-Marie-Tooth 2D, Hereditary motor neuropathy 5A | |
MARS2
| AR | Childhood, adulthood | Autosomal recessive spastic ataxia and leukoencephalopathy (ARSAL) in French Canadians | |
RARS2
| AR | Infancy | Pontocerebellar hypoplasia type 6 | |
SARS2
| AR | Infancy | Tubulopathy (hyperuricemia, metabolic alkalosis), pulmonary hypertension, and progressive renal failure (HUPRA) | |
YARS2
| AR | Childhood, adulthood | MLASA | |
Mitochondrial dynamic network (mitochondrial membrane biogenesis and maintenance) | ||||
Fusion |
MFN2
| AD | Childhood, adulthood | Charcot-Marie-Tooth 2A (CMT2A) (multiple deletions) |
OPA1
| AD | Childhood | Optic atrophy (multiple deletions) | |
OPA3
| AD | Adulthood | Optic atrophy | |
AR | Infancy, childhood | Type III 3-methylglutaconic aciduria, Costeff syndrome | ||
PINK1
| AR | Childhood, adulthood | Juvenile Parkinson Disease | |
Fission |
DNM1L (DRP1) | AR | Infancy | Microcephaly, lactic acidosis, optic atrophy |