Mitochondrial Genome Sequencing and Deletion Analysis

Use

This test is used to diagnose mitochondrial disease that is caused by point mutations, small deletions/duplications or large deletions in the mitochondrial DNA (mtDNA). The test is also useful in assessing variants of uncertain significance in nuclear DNA genes that cause mtDNA deletion syndromes. While some disorders caused by mtDNA mutations only affect a single organ (e.g. the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. Many individuals with mitochondrial disorders display a cluster of clinical features that into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthaloplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes. Mitochondrial DNA deletion syndromes predominately comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may observed in different members of the same family or may evolve in a given individual over time. Inheritance of mitochondrial DNA deletion syndromes can be either autosomal recessive (with progressive external ophthalmoplegia [PEO] and multisystem involvement manifesting during early childhood/adulthood), or autosomal dominant (with less severe, often tissue-specific manifestations [e.g., chronic PEO] developing in later adulthood).