Childhood onset dystonia, chorea or related movement disorder

Gene: COX20

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 9:18 a.m. | Last Modified: 11 Oct 2023, 9:18 a.m.

Panel Version: 3.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

COX20 is associated with autosomal recessive mitochondrial disease, with a definitive classification according to ClinGen. Patients present with a combination of childhood-onset cerebellar ataxia, dystonia, and sensory axonal neuropathy. Dong et al. (2021) report 8 unrelated affected individuals from unrelated families from the eastern Chinese population carrying a founder variant c.41A>G (p.Lys14Arg) in either the homozygous or compound heterozygous state. All patients displayed early onset and slowly progressive deep sensory loss and sensory ataxia. In vitro functional studies performed on the identified variants show that they lead to a loss of function. Otero et al. (2019) also report 4 patients with childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy, who carry the same p.Lys14Arg variant in the compound heterozygous state, and also perform functional studies showing the variant results in absent COX20 expression. Doss et al. (2014) also report 2 siblings with the same neuropathy phenotype, with a different homozygous loss of function variant, c.154A>C (p.Thr52Pro). Knockdown of COX20 results in complex IV deficiency and perturbed assembly of complex IV, as do a number of genes that have been implicated with peripheral neuropathies. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.

Created: 20 Jan 2023, 11:16 a.m. | Last Modified: 20 Jan 2023, 11:16 a.m.

Panel Version: 2.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054

Publications

• 30656193
• 33751098
• 24202787

Red List (low evidence)