heteroplasmia

Heteroplasmy, also spelled heteroplasmia, is a mitochondrial genetic state in which more than one mtDNA sequence is present within a cell, tissue, or organism. In contrast, homoplasmy describes a situation in which all mtDNA copies are identical.

Mitochondria carry multiple copies of mtDNA. Copies are distributed randomly among daughter cells during cell division. Mutations create variant genomes, producing a heteroplasmic mixture. The clinical impact depends on the proportion of mutant genomes, which must exceed a tissue-specific threshold to impair function.

Most mtDNA is inherited from the mother. Heteroplasmy can arise from new mutations or ancestral variation. During oogenesis, a bottleneck reduces and then expands mtDNA copies, yielding variable mutant loads in offspring. Consequently, siblings may differ in disease risk.

Phenotypes range from asymptomatic to multisystem disease, depending on tissue mutant load. Disorders linked to heteroplasmy include LHON, MELAS, and MERRF. Heteroplasmy also contributes to aging changes and somatic mosaicism in cancers and degenerative diseases. Because distribution is tissue-specific, blood levels may not reflect those in muscle or brain.

Detection relies on sequencing mtDNA from affected tissue; next-generation sequencing or sensitive PCR methods quantify mutant load. Because heteroplasmy is tissue-specific, sampling strategy is important; grading severity uses clinical assessment alongside mtDNA heteroplasmy percentage.