Affiliations: [a] Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA
| [b] Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Correspondence to: Nivedita Uberoi Jerath, MD, Department of Neurology, University of Florida, PO Box 10036, Gainesville, FL 32610, USA. Tel.: +1 706 691 9066; Fax: +1 352 627 4175; E-mail: [email protected].
Abstract: Introduction:Mutations in the gene encoding DNA polymerase gamma (POLG) impair its ability to proofread mitochondrial DNA (mtDNA) during replication . This results in a high frequency of randomly distributed mtDNA mutations and thus a wide range of phenotypes, including seizures, neuropathy, and cerebellar ataxia [1, 2]. We document a phenotype associated with the rare POLG variant c.1370G>A (p.R457Q). Methods:Over 10 years, we performed electrodiagnostic and neuropsychologic on a patient who presented with a variety of neurologic symptoms. Results:Testing revealed an axonal sensorimotor polyneuropathy, depression and executive function difficulties, and asymmetric ataxia. Genetic testing revealed a POLG variant of uncertain significance (c.1370G>A, p.R457Q) in a heterozygous state. Conclusions:We have identified a mutation in POLG that could result in a diverse array of symptoms and signs of our patient. However, interpreting pathogenicity of rare variants such as R457Q is challenging and will likely require identification of patients with similar phenotypes caused by the variant of uncertain significance.