Molecular Characteristics for Families

The ATP8A2 gene is highly expressed in the retina, brain, spinal cord, and testis. Within the brain, ATP8A2 is expressed in all regions; the highest levels have been reported in the cerebellum (the region mainly affected in ataxia patients). This gene encodes the protein phospholipid-transporting ATPase IB, which is important for the proper maintenance of the membranes of cells organelles.

In mice, ATP8A2 deficiency induces axonal degeneration (degeneration of the long process of a neuron) and neuronal chromatolysis (a pathological process that cause damage to neurons). Besides that, mice with ATP8A2 mutations in both copies of the gene grow slower, have a reduced lifespan, and develop movement symptoms resembling human disease.

ATP8A2 mutations causing disease are of different types, ranging from the substitution of a single nucleotide (basic building block of DNA) to the loss of several nucleotides.

Studies that analysed differences between “normal” ATP8A2 and mutated ATP8A2 found that the latter could cause a decrease in ATP8A2 levels, change its localization inside the cells and/or inactivate its cellular functions.