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

Calico catX-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.

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.

Pictured, above: a calico cat

 


6 Responses to 'A Surprising Number of Carrier Females are Affected by X-Linked Retinitis Pigmentosa'

  1. LAuren Govan says:

    I have xlrp, and am legally blind. I have alos paseed it onto my 19 yr old daughter. My sister has rp, but her vision is not bad. She has also passed it on to her daughter 29. You may think a stupid ?, but if inactivation has occurred in our girls, can we somehow switch it (the good inactive X, back on to function propely). Can you tell if she has a good X crom that has been affected by inactivation. You never know unless you ask.Thanks.

    • EyeOnTheCure says:

      X-inactivation (also called lyonization) is a process by which one of the two copies of the X chromosome present in females is inactivated. The inactive X chromosome is silenced by its being packaged in such a way that it has a transcriptionally inactive structure called heterochromatin. As nearly all females have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome. The choice of which X chromosome will be inactivated is random, but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell. Preliminary studies indicate that it may be possible that in the future to “reactivate” the inactive chromosome.

    • Sarina says:

      The good X chromosome shut off is shut off during the development of the fetus. It can never be reversed.
      (Source: life science bachelor’s degree)

  2. Carol Carlson says:

    Lauren, my brother has XLRP as do many distant relatives.Unfortunately, X chromosomes can not be reactivated. Each female cell starts out at conception with 2 X’s, but very early in development, each makes an apparently random “decision” to inactivate one X chromosome. Thereafter, in every cell division, the same X will always be deactivated. So, the retinal cells will have different X chromosomes active. If a female is “lucky” enough to have had the RP X shut down in a lot of cells, her vision will be mildly effected. She is likely to have a least some of her retinal cells functioning normally. The deactivated X chromosome is visible as the Barr Body that identifies female cells under a microscope. You can research “lyonization” to learn more. Since the males have only the one RP X in every body cell, they have the more extreme problems. My mother and her sister were both “carriers” ( a misnomer, really, as females technically have XLRP as well, but are usually mildly effected); however, my mother did not know it until my brother was diagnosed at 34, but my aunt had significantly compromised vision almost her entire life.

  3. B. says:

    I know someone has X-Linked RPGR ORF15 , Loss function . DNA change c.2894del , Protein change p.glu965glyfs*124 .

    My questions are : How can you tell if this is X-linked dominant or recessive ?

    Would females be a carrier whether they have dominant or recessive X-Linked RPGR ?

    • EyeOnTheCure says:

      This condition is X-linked recessive. Females can be carriers. Occasionally, they can also be affected. Everyone’s case is unique. Without knowing their family history, it is difficult to speculate who is at risk of being affected or a carrier. Whoever identified the mutation should explain what the results mean for the patient and family. We suggest you contact them.

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