COASY Protein-Associated Neurodegeneration via the COASY Gene

COASY protein-associated neurodegeneration (CoPAN) is a rare type of neurodegeneration with brain iron accumulation (NBIA), type 6. Major features include progressive spasticity and dystonia from early childhood, followed by oro-mandibular dystonia with dysarthria, parkinsonism, axonal neuropathy and cognitive impairment. The COASY gene is in the same metabolic pathway as PANK2, therefore, COASY protein-associated neurodegeneration patients display similar clinical features to Pantothenate kinase-associated neurodegeneration (PKAN) patients (Levi and Finazzi 2914). Hallmark features in brain MRI show iron deposition in the globus pallidus and substantia nigra with hypo intensities (Dusi et al 2014).

Pathogenic variants in COASY are causative for COASY protein-associated neurodegeneration (CoPAN) which is inherited in an autosomal recessive manner. The COASY gene encodes coenzyme A synthase, which is involved in fatty acid metabolism. Coenzyme A synthase is localized to the mitochondrial matrix, and is a bifunctional enzyme catalyzing the final two steps of CoA synthesis (Arber et al 2016). Pathogenic variants in COASY include missense and nonsense only. To date, no large deletions/duplications have been reported (Dusi et al 2014; Human Gene Mutation Database).

COASY protein-associated neurodegeneration (CoPAN) is a rare disorder, and clinical sensitivity cannot yet be estimated. Analytical sensitivity should be high because all pathogenic variants thus far reported are expected to be detected by sequencing.

Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads.

This test provides full coverage of all coding exons of the COASY gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).