It is well known that mitochondrial DNA (mtDNA)–related disorders are clinically heterogeneous, even within the same family.1 This is because in most patients, pathogenic mtDNA mutations are heteroplasmic, that is, a mixture of normal and mutated mtDNAs. Moreover, applying Mendelian terminology to mitochondrial genetics, heteroplasmic mtDNA mutations are recessive in the sense that very high proportions of a mutation are needed before a clinical phenotype becomes manifest. This threshold effect varies among mutation types and is generally higher for transfer RNA (tRNA) mutations than for protein-coding gene mutations or large-scale single deletions.
DiMauro S. Mitochondrial DNA Mutation LoadChance or Destiny?. JAMA Neurol. 2013;70(12):1484-1485. doi:10.1001/jamaneurol.2013.4401