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Didanosine-Associated Retinal Toxicity in a Patient With a Mutation in the CRB1 Gene
Tamara L Lenis1, Benjamin W Botsford1, David Sarraf2
1Retina Service, Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA.
Insights
Didanosine (DDI) can cause retinal toxicity, especially in individuals with a specific CRB1 gene variant. This case suggests genetic factors may increase susceptibility to DDI-induced retinopathy.
Area of Science:
- Ophthalmology
- Genetics
- Pharmacology
Background:
- Didanosine (DDI) is an antiretroviral medication used in HIV treatment.
- Retinal toxicity is a known, though rare, side effect of DDI therapy.
- The CRB1 gene plays a role in retinal structure and function.
Observation:
- A patient on long-term DDI and tenofovir for HIV developed external ophthalmoplegia.
- The patient presented with bilateral pigmentary retinopathy and chorioretinal atrophy.
- Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene.
Findings:
- The patient's retinal findings were associated with a CRB1 gene variant.
- Crumbs homolog 1 (CRB1) protein is crucial for cell polarity and junctions in the retina.
- The CRB1 variant may predispose individuals to DDI-associated retinal toxicity.
Implications:
- Genetic factors, specifically CRB1 variants, may contribute to DDI-induced retinal toxicity.
- Pharmacogenomic studies are needed to identify individuals at higher risk for drug-induced retinal toxicity.
- This finding could inform personalized treatment strategies for HIV patients receiving DDI.
Purpose:
This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.
Methods:
Case report.
Results:
A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area.
Conclusions:
This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.
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