July 30, 2015: POLG mutations in neurologic disease

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July 30, 2015

POLG mutations in neurologic disease

Mutations in the polymerase gamma, or POLG gene are associated with a broadening spectrum of neurologic disease. The gene itself encodes a DNA polymerase within mitochondria and is the only enzyme that can replicate mitochondrial DNA. Mutations in POLG can result in several neurologic conditions with overlapping symptoms of mental retardation, epilepsy, ataxia, neuropathy, myopathy, and liver disease1. POLG associated syndromes include the Alpers syndrome, manifesting as seizures, developmental regression, and liver disease, the ataxia neuropathy spectrum, childhood myocerebrohepatopathy, myoclonic epilepsy with myopathy sensory ataxia, and progressive external ophthalmoplegia. Symptoms should guide molecular testing. Phenotype-genotype correlations are being delineated and distinct clusters of mutations within the POLG gene may predict age of disease onset as well as disease severity2.


  1. Tang S, Wang J, Lee NC, et al. Mitochondrial DNA polymerase γ mutations: an ever expanding molecular and clinical spectrum. J Med Genet 2011; 48: 669-681.
  2. Farnum GA, Nurminen A, and Kaguni LS. Mapping 136 pathogenic mutations into functional modules in human DNA polymerase γ establishes predictive genotype-phenotype correlations for the complete spectrum of POLG syndromes. Biochim Biophy Acta 2014; 1837: 1113-1121.

Submitted by Adam Numis MD, University of California, Los Angeles.

Disclosures: Dr. Numis is a member of the Residents & Fellows Section of Neurology.

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