Abstract
Purpose
To describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified.
Methods
Detailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period.
Results
At presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function.
Conclusions
The p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.
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Abbreviations
- ERG:
-
Electroretinogram
- ISCEV:
-
International Society for Clinical Electrophysiology of Vision
- PST domain:
-
Proline–serine–threonine-rich domain
- RPE:
-
Retinal pigment epithelium
- TID:
-
Transillumination defect
- OD:
-
Right eye
- OS:
-
Left eye
- OU:
-
Both eyes
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Acknowledgments
This study was supported in part by Research to Prevent Blindness, Inc., New York, NY (unrestricted grants to the UTHSC Hamilton Eye Institute and Physician Scientist Award to AI), and the Roger L. Hiatt, M.D. Endowed Chair (NCK). The majority of the diagnostic equipment utilized in this study is a generous donation of the Mid-South Lions, Memphis, TN.
Conflict of interest
The authors have no proprietary interest in the material presented in this report. Dr. Smaoui was an employee of GeneDx at the time that diagnostic PAX6 testing was performed and the manuscript was written.
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Hood, M.P., Kerr, N.C., Smaoui, N. et al. Abnormal cone ERGs in a family with congenital nystagmus and photophobia harboring a p.X423Lfs mutation in the PAX6 gene. Doc Ophthalmol 130, 157–164 (2015). https://doi.org/10.1007/s10633-014-9477-3
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DOI: https://doi.org/10.1007/s10633-014-9477-3