Table 1.

Pathogenic mutations in nuclear genes encoding COX subunits

Gene	DNA change (cDNA)	Protein/RNA change	Mutation	Disease	Cases	Publication
COX4I1	c.303G>T	p.Lys101Asn	homozygous	Fanconi anemia	1	(Abu-Libdeh et al. 2017)
COX4I1	c.454C>A	p.Pro152Thr	homozygous	Leigh syndrome with developmental regression, intellectual disability, and seizures	2	(Pillai et al. 2019)
COX4I2	c.412G> A	p.Glu138Lys	homozygous	Exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis	4	(Shteyer et al. 2009)
COX5A	c.319C>T	p.Arg107Cys	homozygous	Pulmonary arterial hypertension, lactic acidemia	2	(Baertling et al. 2017)
COX6A1	c.247–10_247–6delCACTC	alternative splicing	homozygous	Axonal form of Charcot-Marie-Tooth syndrome	3	(Tamiya et al. 2014)
COX6B1	c.59G>A	p.Arg20His	homozygous	Encephalomyopathy	2	(Massa et al. 2008)
COX6B1	c.58C>T	p.Arg20Cys	homozygous	Encephalomyopathy, hydrocephalus, hypertrophic cardiomyopathy	1	(Abdulhag et al. 2015)
COX7B1	c.196delC c.41-2A>G c.55C>T	p.Leu66Cysfs*48 p.Val14Glyfs*19 p.Gln19*	heterozygous	X-linked microphthalmia with linear skin lesions	3	(Indrieri et al. 2012)
COX8A	c.115-1G>C	aberrant splicing	homozygous	Leigh-like syndrome with leukodystrophy and epilepsy	1	(Hallmann et al. 2016)
NDUFA4	c.42+1G>C	aberrant splicing	homozygous	Leigh syndrome	4	(Pitceathly et al. 2013)