Table 1.

Molecular Genetics of Mitochondrial DNA-Associated Leigh Syndrome Spectrum

Gene 1, 2% of mtDNA-LSS Attributed to Pathogenic Variants in Gene 3, 4Proportion of Pathogenic Variants 5 Identified by Method
Sequence analysis 6Mitochondrial DNA deletion/duplication analysis 7
MT-ATP6 ~40% 8>95%<5% 9
MT-ND3 ~20%
MT-ND5 ~15%
MT-ND6 ~10%
MT-ND4 ~5%
MT-ND1 <5%
MT-TL1 <5%
MT-CO1 Rare
MT-CO2 Rare
MT-CO3 Rare
MT-ND2 Rare
MT-TI Rare
MT-TK Rare
MT-TV Rare
MT-TW Rare

mtDNA-LSS = mitochondrial DNA-associated Leigh syndrome spectrum

1.

Genes are listed from most frequent to least frequent genetic cause of mtDNA-LSS and then alphabetically.

2.
3.

These estimates are based on several cohorts of individuals with mtDNA-LSS, which are likely affected by inclusion criteria, testing strategies, and ascertainment bias [Sofou et al 2014, Bonfante et al 2016, Sofou et al 2018, Wei et al 2018, Yu et al 2018, Alves et al 2020, Hong et al 2020, Lee et al 2020, Ogawa et al 2020, Ardissone et al 2021, Lim et al 2022, Stenton et al 2022, Tinker et al 2022, Ardissone et al 2023, Baldo et al 2023, Kistol et al 2023, Na & Lee 2023].

4.

Data derived from MITOMAP

5.

See Molecular Genetics for information on pathogenic variants detected.

6.

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

7.

Single-gene mtDNA deletions have not been reported. Deletion/duplication analysis of the entire mitochondrial genome may include a range of techniques such as quantitative PCR or long-range PCR.

8.

The most common MT-ATP6 pathogenic variants in individuals with mtDNA-LSS include m.8993T>G, m.8993T>C, m.9176T>C, and m.9185T>C [Ganetzky et al 2019, Stendel et al 2020, Na & Lee 2022].

9.

Large-scale deletions have been reported in individuals with mtDNA-LSS [Yamashita et al 2008, Ardissone et al 2021].

From: Mitochondrial DNA-Associated Leigh Syndrome Spectrum

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