POLG2(polymerase gamma accessory subunit) is a nuclear gene that encodes for the accessory subunit for the mitochondrial DNA polymerase. It enhances DNA binding and DNA replication processivity to the DNA polymerase which is essential for the replication and maintenance of mitochondrial DNA (mtDNA). It is an essential gene but can be haplosufficient.
There are several types of mutations that have been identified in the POLG2 gene, including missense, nonsense, frameshift, and splice site mutations. These mutations can result in a variety of clinical presentations, ranging from infantile-onset encephalopathy to adult-onset progressive external ophthalmoplegia (PEO).
The pathophysiological mechanism underlying POLG2-related diseases is thought to involve defects in mtDNA replication and maintenance, leading to a depletion or accumulation of mtDNA mutations, oxidative stress, and mitochondrial dysfunction.
Diagnostic testing for POLG2-related diseases typically involves genetic testing, such as targeted sequencing or next-generation sequencing, to identify mutations in the POLG2gene. Additionally, biochemical assays may be used to measure mtDNA content and respiratory chain enzyme activities to support the diagnosis. Clinical features such as neurological symptoms, muscle weakness, and developmental delays can also help with diagnosis.
POLG2