Table 3.

Neurological diseases caused by protein variants involved in mitochondrial genome maintenance.

Protein name	Pathogenic mutations or changes	Neurological disorders	References
TWINKLE	p.Ser369Pro, p.Leu381Pro p.Arg354Pro, p.Ala359Thr p.Ile367Thr, p.Val368Ile p.Arg374Gln, p.Ala475Thr	PEO	Korhonen et al. (2008), Liu et al. (2008), and Peter et al. (2019)
	p.Ala318Thr, p.Thr457Ile p.Tyr508Cys	IOSCA Epileptic encephalopathy	Hakonen et al. (2008) and Lonnqvist et al. (2009)
POLγA	p.Ala467Thr, p.Arg597Trp p.Thr748Ser, p.Arg627Trp p.His932Tyr, p.Gly1015Arg p.Arg1096Leu	AHS, MELAS, MEMSA, SANDO	Neeve et al. (2012), Rajakulendran et al. (2016), Abdoh (2019), and Parada-Garza et al. (2020)
	p.Trp748Ser p.Arg964Cys	Neurodegenerative phenotypes, like ataxia, parkinsonism, and seizures	Van Goethem et al. (2003), Luoma et al. (2004), Hakonen et al. (2005), and Hsieh et al. (2019)
p.Ser1181Asn		Neuromyopathic phenotype	Dohrn et al. (2022)
POLγB	p.Asp433Tyr	Optic atrophy, movement disorders	Dosekova et al. (2020)
TFAM	p.Arg232Cys	Seizures, intellectual disability, and hearing loss	Ullah et al. (2021)
	p.Ser12Thr	PD	Alvarez et al. (2008)
Decreased level		HD, AD	Kim et al. (2010) and Kang et al. (2018)
POLRMT	p.Pro566Ser, p.Asp870Asn p.Ser1193Phe, p.His250Asp p.Pro742_Pro747del p.Gly881_Lys883del p.Ser611Phe, p.Phe641Leu p.Cys925*, p.Pro810Ser p.Gln149*, p.Arg1013Cys p.Gln149*, p.Arg1013Cys	Global developmental delay, hypotonia, short stature, and speech/intellectual disability	Oláhová et al. (2021)