Complex IV (CIV or COX, cytochrome c oxidase of the mitochondrial respiratory chain) is a multimeric enzyme complex that contains two redox-active copper centers (CuA and CuB) and two redox-active heme A moieties (heme a and a3). Assembly of complex IV involves several steps. Mutations in at least 4 proteins that are not physical components of Complex IV but play important roles in the assembly of the active complex have been reported in patients with isolated cytochrome c oxidase deficiency. Clinical phenotype is heterogeneous, including Leigh syndrome, fatal infantile hypertrophic cardiomyopathy and myopathy, fatal infantile lactic acidosis and reversible COX deficiency in skeletal muscle. The first such mutations causing failure in complex COX assembly were identified in the SURF1 gene in patients with Leigh syndrome. The exact function of SURF1 has not been established. However, a defect in SURF1 causes the accumulation of the first two sub-assemblies, suggesting that SURF1 is involved in the formation of the third sub-complex. Both SCO2 and SCO1 are involved in copper trafficking and SCO1 is required for the formation of the copper center of heme A. COX10 encodes for heme A:farnesyl-transferase, which is necessary for the proper incorporation of a heme group into complex IV. Molecular defects in any of these genes result in complex IV deficiency. This test includes direct DNA sequencing of SURF1, SCO2, SCO1, and COX10. Reasons for Referral:
Testing Methodology:The exons and flanking intron regions of SURF1, SCO2, SCO1, and COX10 genes are PCR amplified and sequenced. Specimen Requirements:Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc Turnaround Time:4 weeks CPT Codes and Prices:83904x40, 83898x20, 83912x4, 83891, 83894x8 Shipping InformationForms:>> Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included References:
Test Codes:3105 |