Scientists have found that a urine test can help identify a gene mutation that causes an inherited, degenerative disease that results in severe vision impairment and often blindness.
Dr Rong Wen and Dr Byron Lam at the Bascom Palmer Eye Institute in Florida worked with Ziqiang Guan, an associate research professor of biochemistry in the Duke University to analyse cells cultured from a family in which three out of the four siblings suffer from Retinitis pigmentosa (RP).
Guan's team had previously sequenced the genome of this family and found that the children with RP carry two copies of a mutation at the dehydrodolichol diphosphate synthase (DHDDS) gene, which makes the enzyme that synthesises 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, Guan analysed 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.
The parents, who each carry one copy of the mutated DHDDS gene, showed intermediate levels of dolichol-19 and higher levels of dolichol-18 than their healthy child.
Guan believes dolichol profiling could effectively distinguish RP caused by DHDDS mutation from that caused by other mutations.
Guan and his collaborators hope to develop the dolichol profiling method as a first-line diagnostic test to identify RP patients with abnormal dolichol metabolism.
They think this mass spectrometry-based detection method will help physicians provide more personalised care to RP patients, especially to young children whose retinal degeneration has not fully developed.
"Since the urine samples gave us more distinct profiles than the blood samples, we think that urine is a better clinical material for dolichol profiling," he said.
The team is now pursuing a patent for this new diagnostic test for the DHDDS mutation.
"We are now researching ways to manipulate the dolichol synthesis pathway in RP patients with the DHDDS mutation so that the mutated enzyme can still produce enough dolichol-19, which we believe may be important for the rapid renewal of retinal tissue in a healthy individual," Guan said.
The study was published in the Journal of Lipid Research.