MtDNA landscape in South African paediatric patients clinically diagnosed with suspected mitochondrial disorders

Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.The relevance of haplogroups in mitochondrial disease was investigated in this study. Twenty-seven paediatric patients with clinically suspected mitochondrial disorders from diverse ethnic origins were investigated via an automated sequencing strategy. Previous studies in a similar population identified only the A3243G reported causative mutation in a single patient, in addition to a number of reported and unreported polymorphisms. It suggested that the aetiology of mitochondrial disorders in Africa, specifically South Africa, might be different from that of other continents. Comparison between these sequences and the Revised Cambridge Reference Sequence revealed 37 polymorphic sites (7 novel changes, 30 reported alterations). No previously reported causative mutation was detected. The findings support the hypothesis that the aetiology of mitochondrial disorders in Africa is unique. Sixty-three percent of patients in the current study belonged to haplogroup L3 (48% in L3b), 22% to LO, 11% to L2a, and 4% to M. No patients with an L1 haplogroup were observed in this study. The above-mentioned observations have important implications. There was distinct clustering of affected patients in macrohaplogroup L. In this patient cohort, certain sub-haplogroups may play a susceptibility or protective role with regard to mitochondrial dysfunction. Results generated in this study suggested that differential haplogroup-tissue-specific reliance on mitochondrial ATP may culminate in specific phenotypic consequences.Master