What is Choroideremia - Genetics, Diagnosis and Clinical trials

What is Choroideremia?

Choroideremia is a rare inherited disorder of X link recessive retinal disease prevalent in males and is rare among females. The disorder is characterized by progressive loss of vision as a result of choroid and retina degeneration.

Picture 1: Difference between the normal eye and Choroidermia affected eye

image source: news-medical.net

This inherited disorder is a result of deletion of Rab escort protein or REP1. Rab proteins are involved in the movement of proteins and organelles within the cells. Choroideremia gene or CHM is the only gene responsible for choroideremia.

The mutation of CHM results to production of REP1 protein. This result of mutation attaches to Rab protein and inhibits dysfunction in carrying out its function of directing protein and organelles movement within cells.

Choroideremia is an inherited condition of X link recessive pattern. It is an alteration in the copy of the choroideremia gene. The prevalence of disorder in males is due to X chromosome that consists of only one copy and an alteration in one copy of gene is enough to cause this inherited disorder.

Females pass on the mutated copy as they have 2 X chromosome thus; they are referred to as the carrier. Choroideremia can affect females although they do not usually experience the signs and symptoms.

Males suffering for choroideremia can transmit the mutation to all his female offspring and none to male offspring. Female offspring who inherited the mutation will then be carriers and pass it on to their male offspring.

Choroideremia Symptoms

The primary symptom of choroideremia is impairment in night vision or a poor vision in the dark that usually occur during early childhood years. Peripheral vision is loss including depth perception as the disorder progresses usually on the second decade or teen years of male.

All sights are eventually loss by middle age of males. Severe loss of acuity and color perception may occur in some cases as the disorder progresses. The progression of the disorder continues throughout the life of an affected individual.

Mental retardation or reduced ability of mental and intelligence will also manifest. Other symptoms of choroideremia include atrophy of the retinal layers, obesity, progressive loss of vision and blindness.

Obesity and deafness are reported in some cases that manifests with choroideremia. The manifestations however, are uncertain and are thought to be suggestive of other unique disorder that may be associated with choroideremia.

Choroideremia Gene Therapy

Choroideremia is caused by depletion in gene CHM and is an inherited retinal disease. The characteristic of the disorder is a progressive vision loss mostly affecting males. A foundation has been established for research to treat choroideremia

Picture 2: X-Link recessive carier father

image source: http://disorders.eyes.arizona.edu

Therapy of delivering corrective CHM gene has been engineered to cease the progression of the disorder for some years or even lifetime. The therapy is utilizing a genetically engineered virus called adeno-associated virus or the AAV to deliver copies of corrective CHM gene.

Technology of delivering the corrective gene is similar to those used for patient with retinal disease that causes severe vision loss or blindness. The technology and therapy employed is similar to that of the clinical trials for restoring vision for both adults and children.

Picture 3: X-Link recessive carier Mother

images source: perinatology.com

Choroideremia diagnosis

The condition of choroideremia can be detected by ophthalmologist through careful examination utilizing a dilated eye examination and based on the result or presentation of inside of the eye. Genetic analysis may be performed to further evaluate and confirm the existence of choroideremia. Electroretinography of ERG is utilized to confirm choroideremia.

Effective treatment for choroideremia has not been established at present and clinical researches are still underway and on its clinical trial to further determine and establish the effectiveness of the therapy. Visual functions are improved at the moment utilizing a low vision aids.

Choroideremia Research

The discovery of X mutations drove scientists to search for treatment and correcting CHM gene. Gene therapy are now being tried to applied to animal studies for further evaluation and will be moved to clinical studies if found successful.

Clinical trials for gene therapy to treat choroideremia may be established for some years or a couple of years according to some researchers owing to the success of preclinical studies of gene therapy of choroideremia.

Researchers are utilizing the technology of correcting CHM gene by adeno-associated virus similarly used for gene therapy to treat Leber congenital amaurosis.

Families affected with choroideremia are encouraged to seek advice from ophthalmologist and for genetic guidance. Pregnant women of choroideremia inherited may also seek further information and advice after determining the possibility of gene transfer through prenatal consultation.