Table 1

Genetic classification of human mitochondrial disorders

Type of disorderInheritance pattern
*mtDNA nucleotide positions refer to the L-chain, and are taken from the standard Cambridge reference sequence). AD, autosomal dominant; AR, autosomal recessive; M, maternal; S, sporadic; XLR, X linked recessive.
Mitochondrial genetic disorders*
Rearrangements (large scale partial deletions and duplications)
Chronic progressive external ophthalmoplegia (CPEO)S
Kearns-Sayre syndromeS
Diabetes and deafnessS
Pearson marrow-pancreas syndromeS
Sporadic tubulopathyS
Point mutations
Protein encoding genes
    

  • LHON (G11778A, T14484C, G3460A)

M
    

  • NARP/Leigh syndrome (T8993G/C)

M
tRNA genes
    

  • MELAS (A3243G, T3271C, A3251G)

M
    

  • MERRF (A8344G, T8356C)

M
    

  • CPEO (A3243G, T4274C)

M
    

  • Myopathy (T14709C, A12320G)

M
    

  • Cardiomyopathy (A3243G, A4269G, A4300G)

M
    

  • Diabetes and deafness (A3243G, C12258A)

M
    

  • Encephalomyopathy (G1606A, T10010C)

M
rRNA genes
    

  • Non-syndromic sensorineural deafness (A7445G)

M
    

  • Aminoglycoside induced non-syndromic deafness (A1555G)

M
Nuclear genetic disorders
Disorders of mtDNA maintenance
Autosomal dominant progressive external ophthalmoplegia (with 2° multiple mtDNA deletions)
    

  • Mutations in adenine nucleotide translocator (ANT1)

AD
    

  • Mutations in DNA polymerase γ (POLG)

AD or AR
    

  • Mutations in Twinkle helicase (C10orf2)

AD
Mitochondrial neuro-gastrointestinal encephalomyopathy (with 2° multiple mtDNA deletions)
    

  • Mutations in thymidine phosphorylase (TP)

AR
Myopathy with mtDNA depletion
    

  • Mutations in thymidine kinase (TK2)

AR
Encephalopathy with liver failure
    

  • Mutations in deoxyguanosine kinase (DGK)

AR
Primary disorders of the respiratory chain
Leigh syndrome
    

  • Complex I deficiency: mutations in complex I subunits (NDUFS2, 4, 7, 8, and NDUFV1)

AR
    

  • Complex II deficiency: mutations in complex II flavoprotein subunit (SDH)

AR
Leukodystrophy and myoclonic epilepsy
    

  • Complex I deficiency: mutations in complex I subunit (NDUFV1)

AR
Cardioencephalomyopathy
    

  • Complex I deficiency: mutations in complex I subunit (NDUFS2)

AR
Optic atrophy and ataxia
    

  • Complex II deficiency: mutations in complex II flavoprotein subunit (SDH)

AD
Disorders of mitochondrial protein import
Dystonia-deafness
    

  • Mutations in deafness-dystonia protein DDP1 (TIMM8A)

XLR
Disorders of assembly of the respiratory chain
Leigh syndrome
    

  • Complex IV deficiency: mutations in COX assembly protein (SURFI)

AR
    

  • Complex IV deficiency: mutations in COX assembly protein (COX10)

AR
Cardioencephalomyopathy
    

  • Complex IV deficiency: mutations in COX assembly protein (SCO2)

AR
Hepatic failure and encephalopathy
    

  • Complex IV deficiency: mutations in COX assembly protein (SCO1)

AR
    

  • Complex IV deficiency: mutations in protein affecting COX mRNA stability (LRPPRC)

AR
Tubulopathy, encephalopathy, and liver failure
    

  • Complex III deficiency: mutations in complex III assembly (BCS1L)

AR