POLG(polymerase gamma) is a nuclear gene that encodes for the catalytic subunit of mitochondrial DNA polymerase. It is responsible for the replication and maintenance of mitochondrial DNA (mtDNA), which is essential for the proper function of mitochondria.
There are several types of mutations that have been identified in the POLGgene, 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).
A complete list of disease causing mutations in the human POLGgene can be found here: https://tools.niehs.nih.gov/polg/
The pathophysiological mechanism underlying POLG-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 POLG-related diseases typically involves genetic testing, such as targeted sequencing or next-generation sequencing, to identify mutations in the POLGgene. 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.
POLG