Figure 3.

The single deletion of mitochondrial DNA (mtDNA) within the white matter of the dentate nucleus in Kearns-Sayre syndrome (KSS) is pathogenic. A, A single deletion of mtDNA was detected in laser microdissected regions from KSS dentate nucleus white (lane 1) and gray (lane 2) matter using long-range polymerase chain reaction (PCR); lane 3 shows full-length amplified product from control DNA sample (meninges). B, Real-time PCR revealed significantly greater heteroplasmy levels in dentate white and gray matter (P < .001) than the corresponding regions in control tissue in 3 separate experiments. However, heteroplasmy levels in KSS dentate white matter (WM) were higher than the 60% threshold and significantly greater than in gray matter (GM). In primary mtDNA disorders without myelin-associated glycoprotein loss and due to POLG mutations (3 patients), the heteroplasmy level in dentate white matter was less than 60% and significantly less than in KSS. C, Sequencing of the single, large-scale mtDNA deletion extracted from the long-range PCR gel confirms the 3978–base pair (bp) deletion. The mtDNA deletion removed several key genes and occurs at the site of an imperfect 12-bp repeat (highlighted).