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ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement
Mingchu Xu1, Violet Gelowani1, Aiden Eblimit1
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States 2Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States.
Investigative Ophthalmology & Visual Science
|June 13, 2015
Summary
Genetic mutations in the ATF6 gene cause photoreceptor degeneration (PRD), a rare inherited retinal disease. This discovery opens new avenues for understanding and treating retinal degeneration by targeting protein quality control mechanisms.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Photoreceptor degeneration (PRD) is a diverse group of inherited retinal diseases with an unknown genetic cause in many patients.
- Identifying novel genes is crucial for understanding PRD pathogenesis and developing targeted therapies.
Observation:
- A patient with early-onset PRD presented with characteristic macular and ellipsoid zone abnormalities.
- Standard retinal gene panels did not identify the causative mutation.
Findings:
- Whole-exome sequencing revealed biallelic loss-of-function mutations in the ATF6 gene (NM_007348: c.1126C>T and c.1533+1G>C).
- These rare variants lead to premature stop codons and splicing errors, severely impairing ATF6 function.
- ATF6 is expressed in the neuronal cell layers of the retina.
Implications:
- ATF6 is identified as a novel gene implicated in human photoreceptor degeneration.
- Disrupted protein quality control pathways represent a potential new mechanism in retinal degeneration.
- This finding advances the genetic understanding of PRD and suggests therapeutic targets.
