Aug 4, 2015

A Surprising Number of Carrier Females are Affected by X-Linked Retinitis Pigmentosa

Science Education

40 percent of genetically tested XLRP carriers showed a definitive abnormality in at least one of three visions tests.

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X-linked retinitis pigmentosa (XLRP) is an inherited retinal disease causing significant vision loss, sometimes complete blindness, in males. Females are often considered to be unaffected carriers of the condition, with a 50 percent chance of passing XLRP to their sons.

Photo of a calico cat

A calico cat.

However, women can have vision loss from XLRP as well, and an FFB-funded study of 242 XLRP carriers led by Jason Comander, M.D., Ph.D., at the Massachusetts Eye and Ear Infirmary, indicates that it may happen more than previously thought. Results of the study were published in the journal Ophthalmology.

"I thought that most XLRP carriers would be normal. That is the traditional clinical teaching," says Dr. Comander."However, when you put carriers 'under the microscope,' you find retinal abnormalities in most. Usually the abnormalities are mild and don't change quality of life. Only 2.5 percent of XLRP carriers are legally blind."

Dr. Comander and his team found that 40 percent of genetically tested XLRP carriers showed a definitive abnormality in at least one of three visions tests: visual acuity, visual field or dark adaptation.

What XLRP Carriers Can Do

"I recommend that an XLRP carrier try to figure out how much she is affected," says Dr. Comander."Imaging technologies are widely available at retinal-specialist offices that can evaluate the central retina, an area known as the macula, which is where the most severe problems tend to show up.But, again, these are rare in carriers." He suggests a complete work-up for affected women.

For the moderately or severely affected XLRP carrier, Dr. Comander suggests that she consider a supplementation regimen of Vitamin A palmitate, docosahexaenoic acid (DHA) and lutein. He notes, however, that this regimen hasn't been studied in XLRP carrier women. An FFB information packet provides details for the supplementation regimen, which should only be taken under a doctor's supervision.

Why Women May be Affected

In XLRP and other X-linked diseases, the mutated gene is on an X chromosome. Women aren't expected to have vision loss from XLRP because they have two X chromosomes—a healthy X in addition to the X with the mutation. Because men have one X and one Y, they experience severe vision loss if they inherit the X with the mutation from their mothers.

However, some copies of a woman's healthy X chromosome are inactivated as a result of a process aptly called "random X inactivation." That means women can experience vision loss from XLRP because some copies of healthy X chromosomes in the retina are turned off. Because X inactivation is random, there's variability from woman to woman in how much of the retina is affected.

The Calico in Calico Cats Result from X Inactivation

If you've made it this far in the blog post, you may be wondering why I included a photo of a calico cat (above). Well, just about all calico cats are female and, therefore, have two X chromosomes. One X codes for brown coloring and the other for black. The random inactivation of the "brown" X and "black" X is what gives calicos their distinctive splotchy coloring.