Pathogenic mtDNA variants identified in the South African mitochondrial disease cohort
| Gene | Variant | Total number of cases | Number of families represented | Associated disease phenotype(s) | mtDNA haplogroup context where available (#patients) | |
| African ancestry (L) | Other | |||||
| MT-TL1 | m.3243A>G | 37 | 30 | MELAS, MIDD | V (1) | |
| MT-TK | m.8344A>G | 5 | 5 | MERRF | R0a4 (1) | |
| MT-ND1 | m.3460G>A | 2 | 2 | LHON | ||
| m.3635G>A | 1 | 1 | LHON plus | L0a1b1a1(1) | ||
| MT-ND3 | m.10197G>A | 2 | 2 | Leigh syndrome; MELAS | L1c2a3a (1) | U5b2a1b (1) |
| MT-ND4 | m.11778G>A | 16 | 14 | LHON | ||
| MT-ND5 | m.13094T>C | 1* | 1 | Leigh syndrome | L0d1c1a (1) | |
| m.13513G>A | 1 | 1 | Leigh syndrome | |||
| MT-ND6 | m.14484T>C | 7 | 7 | LHON | ||
| m.14459G>A | 2 | 2 | Leigh syndrome | |||
| MT-ATP6 | m.8993T>C/G | 11 | 3 | Leigh syndrome, NARP | H3W (1) | |
| m.9176T>C | 2 | 2 | Leigh syndrome | L2a1a (1) | ||
| Primary mtDNA deletions | Deletion sizes ranging from 3 831 bp to ~9000 bp. (online supplemental table 1) | 22 | 22 | CPEO, KSS, Pearson | ||
| Multiple deletions in muscle (no nDNA change identified to date) | 3 | 3 | ||||
| mtDNA depletion (not part of routine service prior to 2019) | 1 | 1 | Later confirmed as MPV17-related neurohepatopathy | |||
| Total mtDNA positive cases diagnosed | 113 | 96 | ||||
*Previously described in Ng et al. 24
CPEO, chronic progressive external ophthalmoplegia; KSS, Kearns-Sayre syndrome; LHON, Leber’s hereditary optic neuropathy; MELAS, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; MERRF, myoclonic epilepsy with ragged red fibers; MIDD, maternally inherited diabetes and deafness; mtDNA, mitochondrial DNA; NARP, neuropathy, ataxia, and retinitis pigmentosa; nDNA, nuclear DNA.