Heteroplasmy is the presence of a mixture of more than one type of an organellar genome (mitochondrial DNA (mtDNA) or plastid DNA) within a cell or individual. It is a factor for the severity of mitochondrial diseases. Since most eukaryotic cells contain many hundreds of mitochondria with hundreds of copies of mtDNA, it is possible and indeed very frequent for mutations to affect only some mitochondria while others are unaffected. Heteroplasmy can be beneficial rather than detrimental insofar as centenarians show a higher than average degree of heteroplasmy.
Microheteroplasmy is normally found as hundreds of independent mutations in one organism, with each mutation usually found in 1–2% of all mitochondrial genomes. However, the rest of this article primarily focuses on more gross heteroplasmy.
Severity and time to presentation
Symptoms of severe heteroplasmic mitochondrial disorders frequently do not appear until adulthood because many cell divisions and a lot of time is required for a cell to receive enough mitochondria containing the mutant alleles to cause symptoms. An example of this phenomenon is Leber optic atrophy. Individuals with this condition often do not experience vision difficulties until they have reached adulthood. Another example is MERRF syndrome (or Myoclonic Epilepsy with Ragged Red Fibers). In MELAS, heteroplasmy explains the variation in severity of the disease among siblings.
Preimplantation genetic screening (PGS) can be used to quantitate the risk for a child of being affected by a mitochondrial disease. A muscle mutation level of approximately 18% or less generally confers a 95% or higher chance of being unaffected.
One notable example of an otherwise healthy individual whose heteroplasmy was discovered incidentally is Nicholas II of Russia, whose heteroplasmy (and that of his brother) served to convince Russian authorities of the authenticity of his remains.
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