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

Abstract

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. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.