Asymmetric Ataxia, Depression, Memory Loss, Epilepsy, and Axonal Neuropathy Associated with A Heterozygous DNA Polymerase Gamma Variant of Uncertain Significance, c1370G>a (R457Q)

Nivedita U Jerath; Michael E Shy

doi:10.3233/JND-170229

Back

Asymmetric Ataxia, Depression, Memory Loss, Epilepsy, and Axonal Neuropathy Associated with A Heterozygous DNA Polymerase Gamma Variant of Uncertain Significance, c1370G>a (R457Q)

Journal article

Peer reviewed

Asymmetric Ataxia, Depression, Memory Loss, Epilepsy, and Axonal Neuropathy Associated with A Heterozygous DNA Polymerase Gamma Variant of Uncertain Significance, c1370G>a (R457Q)

Nivedita U Jerath and Michael E Shy

Journal of neuromuscular diseases, Vol.5(1), pp.99-104

2018

DOI: 10.3233/JND-170229

PMID: 29278894

View Online

Abstract

Mutations in the gene encoding DNA polymerase gamma (POLG) impair its ability to proofread mitochondrial DNA (mtDNA) during replication [1]. 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). Over 10 years, we performed electrodiagnostic and neuropsychologic on a patient who presented with a variety of neurologic symptoms. 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. 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.

Ataxia - physiopathology

Memory Disorders - physiopathology

Depression - physiopathology

Memory Disorders - genetics

Humans

DNA Polymerase gamma - genetics

Male

Neural Conduction

Epilepsy - physiopathology

Polyneuropathies - physiopathology

Depression - genetics

Disease Progression

Genetic Variation

Polyneuropathies - genetics

Epilepsy - genetics

Heterozygote

Aged

Electromyography

Ataxia - genetics

Executive Function

Details

Title: Subtitle: Asymmetric Ataxia, Depression, Memory Loss, Epilepsy, and Axonal Neuropathy Associated with A Heterozygous DNA Polymerase Gamma Variant of Uncertain Significance, c1370G>a (R457Q)
Creators: Nivedita U Jerath - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Michael E Shy - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Journal of neuromuscular diseases, Vol.5(1), pp.99-104
Publisher: Netherlands
DOI: 10.3233/JND-170229
PMID: 29278894
ISSN: 2214-3599
eISSN: 2214-3602
Language: English
Date published: 2018
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984070666502771

Metrics

30 Record Views