Abstract
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.
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Acknowledgements
We thank the patients and families for their participation, D. Bok for LRAT antiserum, and M. Musarella and A. Swaroop for patient DNA. This study was supported by A. Bernds, The Foundation Fighting Blindness, Deutsche Forschungsgemeinschaft (SFB 430/C2, GA 210/12-1), The National Institutes of Health (EY12298, EY06094, EY07003), The British Retinitis Pigmentosa Association, ProRetina Deutschland American Health Assistance Foundation and Research to Prevent Blindness.
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Thompson, D., Li, Y., McHenry, C. et al. Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy. Nat Genet 28, 123–124 (2001). https://doi.org/10.1038/88828
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DOI: https://doi.org/10.1038/88828
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