Related Experiment Video
Updated: Dec 17, 2025
Author Spotlight: Using the Split Retina Technique for Enhanced Access and Accelerated Experiments
Published on: January 16, 2024
Rod bipolar cell dysfunction in POLG retinopathy
Kit Green Sanderson1, Eoghan Millar2, Anupreet Tumber2
1Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Insights
This study details a child with POLG-related SANDO, highlighting novel electrophysiological findings. An electronegative ERG, indicating rod ON-bipolar dysfunction, was observed for the first time in this disorder.
Area of Science:
- Neurogenetics
- Ophthalmology
- Electrophysiology
Background:
- Mitochondrial DNA polymerase gamma (POLG) mutations cause a spectrum of neurological disorders.
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is a rare POLG-related disorder.
- Understanding genotype-phenotype correlations is crucial for diagnosis and management.
Observation:
- A pediatric patient with a homozygous POLG mutation (c.911T>G/p.Leu304Arg) presented with SANDO features including seizures, hypotonia, and ophthalmoplegia.
- Ophthalmological evaluation revealed reduced visual acuity and bilateral ptosis.
- Serial electroretinography (ERG) demonstrated a markedly reduced b/a ratio and an electronegative configuration in dark-adapted responses.
Findings:
- This is the first report of an electronegative ERG in a POLG-related disorder.
- The electronegative ERG suggests generalized rod ON-bipolar cell dysfunction.
- Clinical features aligned with SANDO but showed overlap with other POLG-related conditions.
Implications:
- The novel ERG finding provides insights into the pathophysiology of POLG-related disorders.
- This case underscores the broad phenotypic variability associated with POLG mutations.
- Electrophysiological studies, particularly ERG, can aid in diagnosing and characterizing POLG-related neurological conditions.
Objective:
To report the clinical and novel electrophysiological features in a child with POLG-related sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO).
Methods:
The proband, a male child of Indian descent, underwent serial systemic and ophthalmological evaluations from birth until 14 years of age. Eye examinations included visual acuity and extraocular movement assessments, fundus photography, spectral domain optical coherence tomography and full-field electroretinography (ERG). Detailed genetic testing was also performed.
Results:
The child carried a homozygous mutation in POLG (c.911T > G/p.Leu304Arg) and manifested systemic features such as seizures, headaches, areflexia, hypotonia, myopathy and vomiting. The child's distance visual acuity was 0.50 and 0.40 LogMAR in the right and left eyes, respectively. Bilateral ophthalmoplegia and ptosis were observed at 5 years of age. The dark-adapted (DA) ERG responses to 2.29 cd s m-2 and 7.6 cd s m-2 stimuli showed a markedly reduced b/a ratio; an electronegative configuration was noted to a DA 7.6 ERG.
Conclusion:
This is the first documented case of an electronegative ERG in a POLG-related disorder consistent with generalized rod ON-bipolar dysfunction. The rest of the proband's systemic and ophthalmological features were consistent with SANDO but some features overlapped with other POLG-related disorders such as Alpers-Huttenlocher syndrome and autosomal dominant progressive external ophthalmoplegia demonstrating the wide phenotypic overlap expected due to POLG mutations.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:32The Retina