Table 1.

Nuclear-encoded cytochrome c oxidase subunit isoform mutations¹.

Gene ID	Type of mutation	Disease phenotypes reported
COX4I2	Human homozygous missense mutation in 4 patients	Exocrine pancreatic insufficiency; dyserythropoietic anemia; calvarial hyperostosis [163]
COX4I2	Mouse homozygous knockout	Reduced airway activity; airway hyporeactivity; lung pathologies [151]
COX6A1	5 bp deletion in a splicing element of intron 2 in two consanguineous families	Charcot-Marie-Tooth disease [204]
COX6B1	Identical homozygous missense mutation in two patients	Infantile encephalomyopathy [181]
COX6B1	Homozygous missense mutation in one patient	Hydrocephalus and cardiomyopathy [182]
COX7B	One patient heterozygous for a 1 bp deletion leading to a frameshift in exon 3; one patient heterozygous for a splice site mutation; one patient with a missense mutation in exon 2	X-linked microphthalmia with linear skin lesions [205]
NDUFA4	Homozygous splice site mutation in four siblings	Leigh syndrome-like [167]
COX8	Homozygous splice site mutation causing frame shift in one patient	Leigh syndrome leukodystrophy and severe epilepsy [202]

¹Note that additional heterozygous mutations have been identified in individual patients with COX deficiency in COX4I2, COX5a, and COX6a2 but have not been functionally confirmed as disease causing [164].