Researchers from the Bascom Palmer Eye Institute of the University of Miami and Duke University are developing a urine test to help determine if the cause of autosomal recessive retinitis pigmentosa (arRP) in Ashkenazi Jews is mutations in the gene DHDDS. While it isn’t a substitute for a diagnosis through genetic testing, the urine test can verify that a given DHDDS mutation is, in fact, causing RP. (Some mutations might be benign.) It can also be used to identify people who are unaffected carriers of DHDDS-associated arRP. Results of the researchers’ related investigation were published in the Journal of Lipid Research.
Keep in mind that several other genes have been linked to retinal degenerations in Ashkenazi Jews, including those in which mutations can cause RP, Usher syndrome and Leber congenital amaurosis. Also, a genetic test — screening a person’s DNA — remains the best method for diagnosing these conditions. If you have any questions about genetic testing, it is best to consult a genetic counselor.
A benefit of the urine test is that it can tell us more about the effect of a DHDDS mutation. The test works by measuring ratios of two lipids. In people with DHDDS mutations — both those with arRP and unaffected carriers — the ratio is different than in those without mutations.
The test might also be helpful in determining the effect of a systemic DHDDS therapy, which would likely bring the lipid ratio to normal throughout the body. However, it would not work for evaluating treatments that were delivered only to the eye (e.g., a gene therapy).
The DHDDS urine test is still only being used in a research setting. The investigators plan to expand its clinical use in the future.
In 2011, Bascom Palmer researchers identified DHDDS mutations as a cause of arRP in Ashkenazi Jews. About 12 percent of arRP in this population is caused by DHDDS mutations. Bascom Palmer scientists have created a mouse model of the condition, and are developing gene and neuroprotective therapies to treat it.
Developers of the DHDDS urine test are Byron Lam, M.D., and Rong Wen, M.D., Ph.D., at Bascom Palmer, and Ziqiang Guan, Ph.D., at Duke.
We’ll be sure to report on additional advancements in DHDDS research as we learn about them.