Purpose: To correlate the molecular characteristics of the mtDNA deletions with clinical phenotypes.
Methods: Southern analysis and polymerase chain reaction (PCR)/DNA sequencing were used to determine the size and location of deletions in 16 patients with mtDNA deletion syndrome. An additional 48 reported cases from the literature were also included in the statistical analysis.
Results: The common 5-kb deletion is found in eight of nine patients with Kearns-Sayre syndrome (KSS), mitochondrial myopathies (MM), or progressive external ophthalmoplegia (PEO). The rare/novel deletions were found in six of seven patients with extra-neuromuscular multisystemic manifestations and infantile/early childhood onset.
Conclusions: Patients with mtDNA deletion syndrome who manifest non-neuromuscular multisystemic disorders at a very young age usually harbor mutant mtDNA with novel or rare deletions in every tissue analyzed. For this group of patients, it is possible to use the less invasive blood specimens instead of muscle biopsies for molecular diagnosis. Overwhelmingly, the common 5-kb deletion is mostly seen in the muscle specimens of patients with KSS and age of onset after the second decade of life.