New Gene Linked to X-Linked Retinitis Pigmentosa

November 28, 2012
A research team led by investigators from University College London (UCL) has found that a defect in the gene OFD1 causes X-Linked retinitis pigmentosa (XLRP), a retinal disease characterized by progressive and severe vision loss. OFD1 is the third gene to be linked to XLRP; the other two genes are RPGR and RP2. The latest finding will help researchers diagnose more people affected by XLRP and also identify potential targets for treatments. UCL’s discovery was recently reported in the journal Human Molecular Genetics.

Mutations in OFD1 were previously linked to severe syndromic diseases, such as Joubert syndrome and orofaciodigital syndrome-1, which affect several parts of the body. These conditions are known as ciliopathies, because they affect cells in the body which have tiny hair-like protrusions called cilia. Cilia are found in lungs, kidneys and the inner ear, and play a critical role in the body’s development. Some cilia transport fluids and mucous. Others provide a sensory function. Photoreceptors in the retina — the sensory cells that make vision possible by converting light into electrical signals — are cilia.

The UCL researchers report that, in the case of the mutation in OFD1 that causes XLRP, the gene is not completely shut down and still contributes to the production of about 40 percent of the normal level of protein. The mutation only affects the retina, which is particularly sensitive to changes in cell metabolism. Other defects in OFD1 can have a more dramatic impact on protein production, resulting in severe syndromic conditions.

The OFD1 defect causing XLRP was challenging to find because it was discovered in an intron, a genetic region where disease-causing mutations are less likely to occur. Disease-causing defects are usually found in exons, which provide the code for producing proteins. The role of introns, on the other hand, is to separate exons, and they are discarded at an early stage of the protein-encoding process.

Thus far, the XLRP-causing mutation in OFD1 has been found in only one family. While the UCL researchers believe the mutation is rare, they think it will be found in other families.

XLRP primarily affects males. Women are carriers of the condition, but can occasionally experience vision loss from it as well.