COENZYME Q10 DEFICIENCY
PDSS1 Sequencing
MITOCHONDRIAL DNA ANALYSIS
Also see: Coenzyme Q10 Deficiency - COQ2 Sequencing; Coenzyme Q10 Deficiency - PDSS2 Sequencing

Description:

Coenzyme Q serves as a redox carrier in the mitochondrial respiratory chain and is a lipid-soluble antioxidant. CoQ10 transfers reducing equivalents from various dehydrogenases to complex III (ubiquinone cytochrome c reductase) and acts as a transmembrane hydrogen carrier. Primary coenzyme Q10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder with 3 major clinical presentations: (1) an encephalomyopathic form, characterized by exercise intolerance, mitochondrial myopathy, myoglobinuria, epilepsy, and ataxia; (2) a generalized infantile variant with severe encephalopathy and renal disease; and (3) an ataxic form, dominated by ataxia, seizures, cerebral atrophy, and/or anomalies of the basal ganglia. Q10 deficiency can be caused by mutations in mitochondrial parahydroxybenzoate-polyprenyltransferase (COQ2), prenyl diphosphate synthase, subunit 1( PDSS1), prenyl diphosphate synthase, subunit 2 ( PDSS2), and APTX gene. PDSS1 is the microsomal enzyme that elongates the prenyl side-chain of Q10, which has a role in oxidative phosphorylation within mitochondria, in scavenging free radicals, and in the redox control of cell signaling. Both PDSS1 and PDSS2 are required for the generation of prenyl diphosphate synthase. Humans possess a heterotetrameric prenyl diphosphate synthase composed of PDSS1 and PDSS2 gene products that produces Q10. If there is biochemical evidence of Q10 deficiency or complex III deficiency, DNA analysis of the relevant genes can be performed to confirm the diagnosis. PDSS1 gene maps to chromosome 10p12.1. It contains 12 coding exons, and encodes for a protein of 415 amino acids.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing
Prenatal diagnosis for known familial mutations

Testing Methodology:

The exons and flanking intronic regions of the PDSS1 gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83891, 83904x24, 83898x12, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal Requisition

References:

1. Mollet J, Giurgea I, Schlemmer D, et al. Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH- benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J. Clin. Invest. 2007;117:765–772.
2. Rötig A, Appelkvist EL, Geromel V, et al. Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 2000; 356: 391–95.
3. Saiki, R.; Nagata, A.; Kainou, T.; Matsuda, H.; Kawamukai, M. Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans. FEBS J. 2005; 272: 5606-5622.

Test Codes:

Index: 3405
Known Familial Mutation: 3406
Prenatal: 3407