SURF1 Mutation Analysis
The cytochrome c oxidase complex is composed of 13 subunits that reside in the inner mitochondrial membrane. Three of these subunits, which form the catalytic core of the complex, are encoded by mitochondrial DNA, whereas the remaining 10 subunits are encoded by nuclear DNA. COX catalyzes the terminal step in electron transport, resulting in the reduction of molecular oxygen by reduced cytochrome c. Multiple mutations have been identified in several COX subunits, including all three mitochondrial-encoded subunits, resulting in COX deficiency and disease. Leigh syndrome is an early onset, fatal neurodegenerative disorder characterized by progressive deterioration of the brain stem, basal ganglia and spinal cord. Mutations in SURF1, which functions in the assembly of COX, have been identified in patients with Leigh syndrome and COX deficiency and account for 26-75 percent of Leigh syndrome-COX patients. Leigh syndrome-COX patients with SURF1 mutations typically exhibit only 10-25 percent of COX activity in comparison to normal control individuals.
SURF1 is composed of nine exons, all of which are coding. A variety of autosomal recessive SURF1 mutations have been described in Leigh syndrome-COX patients, including nonsense, splicing and small deletion or insertion mutations, which result in premature protein truncation. Several missense mutations have also been reported. These mutations occur throughout all nine exons of the SURF1 gene.
The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for SURF1 mutations. Symptomatic individuals are tested by automatic fluorescent DNA sequencing of all nine exons of the SURF1 gene. Genetic counseling is recommended for all individuals and their families.
Reasons for Referral
- Molecular confirmation of the diagnosis of Leigh syndrome with COX deficiency
Genomic DNA is analyzed for SURF1 mutations by automatic fluorescent DNA sequencing of all nine exons of the SURF1 gene, as well as the exon/intron junctions, and a portion of the 5' and 3' untranslated regions. Patient DNA is sequenced in both the forward and reverse orientations.
|Service||Direct and Institutional Billing||CPT Codes|
|Index Case (Male or Female)||$750 per sample||81405, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in exons 1-9 of SURF1.
Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek