A new Duke University study suggests that a biomarker in urine is linked to gene mutations that cause retinitis pigmentosa, or RP, an inherited, degenerative disease that results in severe vision impairment or blindness. The findings appear online in the Journal of Lipid Research.
Researchers analyzed cells cultured from a family in which three out of the four siblings suffer from RP. The genome of this family had previously been sequenced, and it was found that the children with RP carry two copies of a mutation at the dehydrodolichol diphosphate synthase (DHDDS) gene, which makes the enzyme that synthesizes organic compounds called dolichols. In humans, dolichol-19, containing 19 isoprene units, is the most abundant species.
The DHDDS mutation, which was found in 2011, is the latest addition to more than 60 gene mutations that have been implicated in RP. This mutation appears to be prevalent in RP patients of the Ashkenazi Jewish origin, and 1 in 322 Ashkenazi carries one copy of the mutation.
Using liquid chromatography and mass spectrometry, researchers analyzed urine and blood samples from the six family members and found that instead of dolichol-19, the profiles from the three siblings with RP showed dolichol-18 as the dominant species. They believe dolichol profiling could effectively distinguish RP caused by DHDDS mutation from that caused by other mutations, and hope to develop the dolichol profiling method as a first-line diagnostic test to identify RP patients with abnormal dolichol metabolism. Read the study abstract.