Aberrant dolichol chain lengths as biomarkers for retinitis pigmentosa caused by impaired dolichol biosynthesis.

Journal Article (Journal Article)

We observed a characteristic shortening of plasma and urinary dolichols in retinitis pigmentosa (RP) patients carrying K42E and T206A mutations in the dehydrodolichol diphosphate synthase (DHDDS) gene, using liquid chromatography-mass spectrometry. Dolichol-18 (D18) became the dominant dolichol species in patients instead of dolichol-19 (D19) in normal individuals. The D18/D19 ratio was calculated and used as an index of dolichol length distribution. K42E/K42E and K42E/T206A patients have significantly higher plasma and urinary D18/D19 ratios than K42E and T206A carriers. The ratios of carriers are significantly higher than normal individuals. Receiver operating characteristic (ROC) analysis shows that plasma and urinary D18/D19 ratios can unambiguously discriminate patients from carriers, and carriers from normal individuals. Dolichol analysis also provides evidence that the T206A mutation is RP-causative. The methodologies and procedures used for dolichol profiling are reliable, high throughput, and cost effective. Dolichol profiling, complementary to genotyping, can be readily adapted as a test in the clinic not only for the diagnosis of patients but also for identification of carriers with DHDDS or other genetic mutations that may impair dolichol biosynthesis.

Full Text

Duke Authors

Cited Authors

  • Wen, R; Lam, BL; Guan, Z

Published Date

  • December 2013

Published In

Volume / Issue

  • 54 / 12

Start / End Page

  • 3516 - 3522

PubMed ID

  • 24078709

Pubmed Central ID

  • PMC3826697

Electronic International Standard Serial Number (EISSN)

  • 1539-7262

Digital Object Identifier (DOI)

  • 10.1194/jlr.M043232


  • eng

Conference Location

  • United States