These deleted molecules have been associated with a number of rare diseases including (but not limited to) Kearns-Sayre Syndrome (KSS)36,37, chronic progressive external ophthalmoplegia (CPEO) with or without an associated POLG mutation37,40,41, and diffuse leukodystrophy39; moreover, they have been found to be enriched in metabolically-active, somatic tissues and have been investigated in pathogenic phenotypes associated with cellular aging (e.g., PD, AD)42–44. Here, POLG is linked to External ophthalmoplegia.