BRIEF DESCRIPTION
DHDDS-related retinitis pigmentosa (RP) 59 is a rare genetic disorder that causes the retina to degenerate. DHDDS stands for dehydrodolichyl diphosphate synthase, a gene that encodes a subunit of the enzyme cis-prenyltransferase (CPT). CPT is required for the synthesis of dolichol, which is a protein glycosylation cofactor. RP59 is caused by a recessive mutation in the DHDDS gene, which changes the 42nd amino acid of the DHDDS enzyme from lysine to glutamic acid. This change is known as a K42E point mutation. RP59 causes the rod cells in the retina to break down first, which typically leads to loss of night vision in childhood. As the disease progresses, blind spots develop in peripheral vision, which eventually merge to create tunnel vision. Finally, central vision gradually declines. RP59 affects one in 100 Ashkenazi Jewish people and one in 2,009 people worldwide.
At present, there is no cure for RP, but medications can help treat complications. A medical professional can diagnose and manage RP to improve symptoms.
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Retinal Degeneration Caused by Rod-Specific Dhdds Ablation Occurs without Concomitant Inhibition of Protein N-Glycosylation
Dehydrodolichyl diphosphate synthase (DHDDS) catalyzes the committed step in dolichol synthesis. Recessive mutations in DHDDS cause retinitis pigmentosa (RP59), resulting in blindness. We hypothesized that rod photoreceptor-specific ablation of Dhdds would cause retinal degeneration due to diminished dolichol-dependent protein N-glycosylation.
Knockdown of Dehydrodolichyl Diphosphate Synthase in the Drosophila Retina Leads to a Unique Pattern of Retinal Degeneration
Tal Brandwine, Reut Ifrah, Tzofia Bialistok, Rachel Zaguri, Elisheva Rhodes-Mordov, Liliana Mizrahi-Meissonnier, Dror Sharon, Vladimir L. Katanaev, Offer Gerlitz, Baruch Minke | Frontiers in Molecular Neuroscience | 2021 05 July |
Dehydrodolichyl diphosphate synthase (DHDDS) catalyzes the committed step in dolichol synthesis. Recessive mutations in DHDDS cause retinitis pigmentosa (RP59), resulting in blindness. We hypothesized that rod photoreceptor-specific ablation of Dhdds would cause retinal degeneration due to diminished dolichol-dependent protein N-glycosylation.
A Missense Mutation in DHDDS, Encoding Dehydrodolichyl Diphosphate Synthase, Is Associated with Autosomal-Recessive Retinitis Pigmentosa in Ashkenazi Jews
Lina Zelinger, Eyal Banin, Alexey Obolensky, Liliana Mizrahi-Meissonnier, Avigail Beryozkin, Dikla Bandah-Rozenfeld, Shahar Frenkel, Tamar Ben-Yosef, Saul Merin, Sharon B. Schwartz, Artur V. Cideciyan, Samuel G. Jacobson, Dror Sharon | AJHG| 2011 Feb 11 | 88(2) | 207–215 |
Using homozygosity mapping in Ashkenazi Jewish (AJ) patients with autosomal-recessive RP (arRP), we identified a shared 1.7 Mb homozygous region on chromosome 1p36.11. Sequence analysis revealed a founder homozygous missense mutation, c.124A>G (p.Lys42Glu), in the dehydrodolichyl diphosphate synthase gene (DHDDS) in 20 AJ patients with RP of 15 unrelated families. . . DHDDS is a key enzyme in the pathway of dolichol, which plays an important role in N-glycosylation of many glycoproteins, including rhodopsin. Our results support a pivotal role of DHDDS in retinal function and may allow for new therapeutic interventions for RP.