Abstract
A single-nucleotide mutation in the gene that encodes DHDDS has been identified by whole exome sequencing as the cause of the non-syndromic recessive retinitis pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four siblings have early onset retinal degeneration. The peripheral retinal degeneration in the affected siblings was evident in the initial examination in 1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly. The identified mutation changes the highly conserved residue Lys42 to Glu, resulting in lower catalytic efficiency. Patterns of plasma transferrin isoelectric focusing gel were normal in all family members, indicating no significant abnormality in protein glycosylation. Dolichols have been shown to influence the fluidity and of the membrane and promote vesicle fusion. Considering that photoreceptor outer segments contain stacks of membrane discs, we believe that the mutation may lead to low dolichol levels in photoreceptor outer segments, resulting in unstable membrane structure that leads to photoreceptor degeneration.
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Acknowledgments
We thank Drs. Yiwen Li and Zhengying Wang for technical assistance. This study was supported by grants from the National Institute of Health (P30-EY14801, R01-EY012118, R01-EY018586, and U54-NS065712), Department of Defense (W81XWH-09-1-0674), Hope for Vision, an unrestricted grant from Research to Prevent Blindness, and a grant from the Florida Office of Tourism, Trade and Economic Development (OTTED).
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Lam, B. et al. (2014). Mutation K42E in Dehydrodolichol Diphosphate Synthase (DHDDS) Causes Recessive Retinitis Pigmentosa. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_21
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DOI: https://doi.org/10.1007/978-1-4614-3209-8_21
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