Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme.
Here we show that overexpression of COX15, a protein involved in the synthesis of heme A, the heme prosthetic group for COX, can functionally complement the isolated COX deficiency in fibroblasts from a patient with fatal, infantile hypertrophic cardiomyopathy.
Mutations in SCO2 have been associated with severe COX deficiency and early-onset fatal infantile hypertrophic cardiomyopathy, encephalopathy, and neurogenic muscle atrophy.
Recently, we and others have shown that mutations in SCO2 are associated with a lethal infantile hypertrophic cardiomyopathy (HCMP) with COX-deficiency.
Here we show that expression of COX10 from a retroviral vector complements the COX deficiency in a patient with anemia and Leigh Syndrome, and in a patient with anemia, sensorineural deafness and fatal infantile hypertrophic cardiomyopathy.