ABSTRACT
The 8993 mutation was first described by Holt and colleagues [1] in a family with a maternally inherited neurodegenerative disease in three generations. The major phenotype was of neurogenic muscle weakness, ataxia and retinitis pigmentosa, and this led to the acronym NARP. The 8993 T-to-G mutation is now referred to as the NARP mutation. Tatuch and colleagues in 1992 [2] reported the occurrence of this mutation in an infant who died at 7 months and at autopsy had the typical neuropathology of Leigh syndrome. It is now clear that 8933 mutation is a common cause of Leigh syndrome [3]. A second mutation at position 8993 changing T to C in the ATPase 6 gene was identified in a family with Leigh syndrome [4]. It was noted early that the percentage of mutant mitochondrial DNA varied considerably in heteroplasmic affected individuals, and this leads to considerable variability in phenotypic expression [5].
