Table 1a.

Molecular Genetics of Mitochondrial DNA-Associated Leigh Syndrome and NARP: Most Common Genetic Causes

Gene 1, 2% of mtDNA-Associated Leigh Syndrome (LS) or NARP Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
MT-ATP6 mtDNA-assoc LS~50% 6>95%<5% 7
NARP>50% 8>95%None
MT-ND3 mtDNA-assoc LS21 individuals 9>95%None
MT-ND5 mtDNA-assoc LS48 individuals 10>95%None
MT-ND6 mtDNA-assoc LS22 individuals 11>95%None
NARP1 individual>95%None

Pathogenic variants in the genes included in this table account for >1% of mtDNA-associated Leigh syndrome and NARP.


Genes are listed alphabetically.


See Molecular Genetics for information on pathogenic variants detected.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small deletions/insertions and missense and nonsense variants; typically, larger deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Single-gene deletions have not been reported in mtDNA disease so deletion/duplication analysis is typically targeted to the entire mitochondrial genome. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a microarray designed to detect deletions or duplications in the mtDNA genome.


Of 106 individuals with Leigh or Leigh-like syndrome, ten of the 30 individuals with mtDNA pathogenic variants had variants in MT-ATP6 [Ogawa et al 2017].


The variant m.8993T>G is most common; m.8993T>C has also been described [Rantamäki et al 2005].


Total of 22 reported probands: 14 probands with m.14487T>C (1 of whom had NARP), five probands with m.14459G>A, one with m.14600G>A; one with m.14439G>A, and an additional proband with no specified variant [Kirby et al 2000, Funalot et al 2002, Lebon et al 2003, Ugalde et al 2003, Bugiani et al 2004, Malfatti et al 2007, Naess et al 2009, Wang et al 2009, Dermaut et al 2010, Leshinsky-Silver et al 2011, Ronchi et al 2011, Tarnopolsky et al 2013, Uehara et al 2014, Han et al 2015]

From: Mitochondrial DNA-Associated Leigh Syndrome and NARP

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