What is Choroideremia?
Choroideremia affects about 1 in 50,000 individuals and is caused by a genetic defect in one single gene called the CHM gene, which is located on the X-chromosome.
Male patients manifest the severe blinding form of the disease and suffer from a progressive retinal degeneration with obliteration of the light sensing cells (photoreceptors), their support cells (the retinal pigment epithelium) and part of the blood supply to these retinal layers (the choroid).
The healthy orange retina is lost and the pale white sclera (tough white coat of the eye) can be seen when you look into the eye. Females are carriers and largely unaffected, however they can develop mild symptoms of visual impairment, such as night blindness, in more in later stages of life.
An affected parent has a 50% chance of passing the defective CHM gene to their children, although as it is positioned on the X-chromosome, affected males can only pass the disease gene to their daughters (so they become carriers) and not their sons. Female carriers have a 50% risk of passing the disease to their sons.
The CHM gene and how it works
The CHM gene encodes a protein called Rab Escort Protein-1 (REP1). This protein works in all our cells by helping to shuttle other small proteins (called Rabs) to their correct destination so they can undertake their role, such as allowing nutrients to pass across cells and removal of waste products.
If these small proteins cannot be transported to their correct location to fulfill their job, the cells can starve and waste products build up causing damage and cell death. Humans are fortunate to have a second copy of REP1 called Rab Escort Protein-2 (REP2), which works well to transport Rabs in all the cells of our body except for the retina.
The photoreceptors and retinal pigment epithelium have a subset of Rab proteins that prefer to be escorted by REP1 over REP2. Therefore, in the presence of a defective CHMgene with lack of REP1, there is a buildup of Rabs that are not able to function appropriately, and this leads to a retinal-specific disease that causes blindness in an otherwise fit and healthy individual……
Source: News Medical