Low-Level Heteroplasmic Single Large mtDNA Deletions Associated with Mitochondrial Electron Transport Chain Enzyme Defects

INTRODUCTION

• Large deletions in mitochondrial DNA (mtDNA) are associated with single large-scale mtDNA deletion syndromes (SLSMDSs), including chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), and Pearson syndrome (PS).
• CPEO and KSS are characterized by a spectrum of symptoms including ptosis, ophthalmoplegia, and mitochondrial myopathy, whereas PS presents with early-onset anemia or pancytopenia in infancy, along with multisystem involvement.
• SLSMDSs often arise from sporadic mtDNA deletions that present in a heteroplasmic state. While the level of heteroplasmy and tissue distribution of the deletions are reported to be determining factors for disease severity, a clear mechanism behind the genotype-phenotype correlation has not been previously documented.