Alternative, Noninvasive Tissues for Quantitative Screening of Mutant Mitochondrial DNA

摘要: Since the molecular basis of first mitochondrial DNA (mtDNA) disorder, Leber hereditary optic neuropathy (LHON), was established (1), mtDNA mutations have become increasingly more recognized as an important cause genetic disease. The most common identified are A3243G, A8344G, T8993G/C, G11778A, and large deletions. A3243G mutation accounts for 80% patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) (2), A8344G MERRF (myoclonic epilepsy ragged-red fibers) (3)(4). Substitution T8993 G or C causes NARP (neuropathy, ataxia, retinitis pigmentosa) (5)(6), G11778A is responsible >50% LHON (1). MtDNA deletions rearrangements found in Kearns–Sayre syndrome chronic progressive external ophthalmoplegia patients. Most pathogenic heteroplasmic, normal mutant coexisting same cell tissue. phenotypic expression a depends on tissue-specific energy requirements (7). Accordingly, age onset, tissues involved, clinical severity vary greatly between individuals, even within given family, depending proportions mtDNA. Direct analysis allows identification asymptomatic relatives who harbor Prediction future disease assisted by quantitative determination proportion relevant tissues. DNA-based diagnosis disorders has been routinely performed blood biopsied skeletal muscle (8)(9). Because variation percentage among different tissues, may not be detectable blood. Nevertheless, it difficult to justify obtaining biopsies from multiple at-risk family members. In this setting, examination alternative such cheek cells hair follicles especially relevant. Studies heteroplasmy …