Genetic Classification of Mitochondrial Disorders 

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Mitochondrial DNA:

• DNA Structure: Mitochondrial DNA is a circular double strand DNA molecule with 16,569 base pair and no introns. Each mitochondrion contains 2-10 copies. The mtDNA genes encode 13 structural proteins in the mitochondrial respiratory chain, 22 tRNA genes required for mitochondria protein synthesis and two 12S and 16S rRNA genes. It has neither DNA repair mechanism nor protective histones.

• Mutation rate: Mutation is 10 times more frequent than nuclear DNA and the coding sequence is always affected since no intron is present. [Vogel H, 2001]. Most mitochondrial diseases are heteroplasmic (normal and abnormal genomes in the same mitochondrion).

List of mutations in mitochondrial encephalomyopathies [Neuromuscular disorder 2001 11:230-235]

Mutation in mtDNA Head

Point mutations

• MELAS (Myopathy, encephalopathy, lactic-acidosis, and stroke like episodes)

• MERRF (Myoclonus epilepsy, ragged-red fibers)

• LHON (Leber's hereditary optic neuropathy)

• NARP (Neuropathy, ataxia, and retinitis pigmentosa)

• Some cases of Leigh's disease

Deletions

• KSS (Kearns-Sayre syndrome)

• CPEO (Chronic progressive external ophthalmoplegia)

Mutation in nuclear DNA Head

Producing deletions of mtDNA

• mtDNA breakage syndrome

• Some cases of MNGIE (myoneurogastrointestinal encephalopathy)

Producing depletion of mtDNA

• mtDNA depletion syndrome

  For Comment: KarMing-Fung@ouhsc.edu