Hereditary Neuropathy_CMT - isolated

Gene: COX20

Green List (high evidence)

Well established association with mitochondrial disease, presentation with neuropathy reported PMID 33751098

Created: 4 Oct 2021, 6:47 a.m. | Last Modified: 4 Oct 2021, 6:47 a.m.

Panel Version: 1.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neuropathy

Publications

• 33751098

Green List (high evidence)

Eight unrelated families carried the Chinese Han founder variant c.41A>G., p.(Lys14Arg) in either homozygous or compound heterozygous state with another variant. (This variant is predicted to cause aberrant splicing by abolishing the donor splice site of exon 1).
Three homozygous for p.(Lys14Arg), two compound heterozygous with p.(Trp74Cys), the others with p.(Ser33Leu), c.157+7A>G, or p.(Gln87*)
All patients displayed sensory ataxia, with early to juvenile age of onset from 1 to 17 years.
The clinical presentations of these patients showed some overlap in central and peripheral nervous systems. They presented with predominant proprioceptive sensory loss and sensory ataxia rather than a multisystem neurological impairment. Initial symptoms: difficulty walking, bilateral foot deformity.
Patient’s fibroblasts and transfected cell lines showed reduction of COX20 protein consistent with a loss-of-function mechanism, and reduced complex IV assembly, enzyme activity and oxygen consumption rate which is consistent with mitochondrial dysfunction..
Sources: Literature

Created: 4 Oct 2021, 4:52 a.m. | Last Modified: 4 Oct 2021, 4:53 a.m.

Panel Version: 1.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
sensory neuronopathy; sensory neuron disease; ganglionopathy

Publications

• PMID: 33751098