Mitochondrial DNA (mtDNA) deletions are a major cause of chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS). We analyzed single mtDNA deletions in 11 CPEO and one KSS patients by means of Southern blot and long polymerase chain reaction (PCR) assays. The deletion sizes ranged from 3.4 kb to 6.9 kb whereas the heteroplasmy level varied from 18.8% to 85.5%. Two unique deletions sized 4320 bp and 4717 bp were found. This study represents the first genetic screen of mtDNA disorders in Malaysia, and it follows the data seen in other published reports on CPEO and KSS genetic aetiology.

A cohort of Malaysian patients with clinico-pathological diagnosis of three specifi c mitochondrial encephalomyopathy syndromes comprising of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy with ragged-red fi bers (MERRF) and Leigh syndrome were studied to determine the frequency of their common mitochondrial DNA mutations. The ‘hot-spot’ point mutations for MELAS, MERRF and Leigh syndrome were screened. In the absence of common point mutations, screening of large-scale deletions as well as sequencing of tRNALeu and tRNALys genes were performed. Of 22 patients studied, nine m.3243A>G mutations, four m.8344A>G mutations, one m.8993T>G mutation and one deletion were identifi ed (65% detection rate). While the m.3243A>G mutation was closely associated with MELAS, the m.8344A>G was more heterogenous, being seen in one MERFF, two isolated mitochondrial myopathies and one Leigh syndrome patient. Screening for m.8993T>G in Leigh syndrome has a low yield as unsurprisingly Leigh syndrome has considerable genetic heterogeneity.