Table 2.2.

Nuclear genes with pathogenic variants that cause mitochondrial progressive external ophthalmoplegia

Gene	Protein	PEO Phenotype	Inheritance	Reference
TYMP	Thymidine phosphorylase	MNGIE	AR	Nishino et al. (2000)
SLC25A4	Adenine nucleotide translocator 1	PEO	AD/AR	Kaukonen et al. (2000)
TK2	Thymidine kinase 2	PEO/PEO-plus	AR	Saada et al. (2001) and Garone et al. (2018)
DGUOK	Deoxyguanosine kinase	PEO	AR	Mandel et al. (2001) and Ronchi et al. (2012)
POLG	Polymerase gamma catalytic subunit	PEO/PEO-plus/SANDO/MNGIE-like	AD/AR	Van Goethem et al. (2001) and Van Goethem et al. (2003a)
TWNK	Twinkle	PEO	AD/AR	Spelbrink et al. (2001)
POLG2	Polymerase gamma subunit 2	PEO	AD/AR	Longley et al. (2006)
RRM2B	P53-subunit of ribonucleotide reductase	PEO/KSS/MNGIE-like	AD/AR	Bourdon et al. (2007) and Pitceathly et al. (2012)
OPA1	GTPase mitochondrial fusion	PEO-plus	AD	Hudson et al. (2008)
MGME1	Mitochondrial genome maintenance exonuclease 1	PEO/KSS	AR	Kornblum et al. (2013)
DNA2	DNA replication ATP-dependent	PEO	AD	Ronchi et al. (2013)
SPG7	Paraplegin	PEO-plus	AR	Wedding et al. (2014)
AFGL2	AFG3-like protein 2	PEO-plus	AD	Gorman et al. (2015)
RNASEH1	Ribonuclease H1	PEO/PEO-plus	AR	Reyes et al. (2015) and Bugiardini et al. (2017)
C1QBP	Complement component C1q binding protein	PEO	AR	Feichtinger et al. (2017)
TOP3A	DNA topoisomerase 3 alpha	PEO-plus	AR	Nicholls et al. (2018)
GMPR	GMP reductase 1	PEO	AD	Sommerville et al. (2020)
LIG3	Ligase III	MNGIE-like	AR	Bonora et al. (2021)
RRM1	Ribonucleotide reductase catalytic subunit	PEO/MNGIE-like	AD/AR	Shintaku et al. (2022)

Abbreviations: AD, autosomal dominant; AR, autosomal recessive; KSS, Kearns–Sayre syndrome; MNGIE, mitochondrial neurogastrointestinal encephalomyopathy; PEO, progressive external ophthalmoplegia; SANDO, sensory ataxic neuropathy dysarthria ophthalmoplegia.