Choroideremia (CHM; OMIM 303100) is an X-linked recessive retinal degeneration characterized by a progressive degeneration of photoreceptors, retinal pigment epithelium (RPE), choriocapillaris and eventually the choroid. Female carriers show scattered pigment deposits or focal areas of RPE atrophy. CHM is caused by mutations in the REP1 gene, which is ubiquitously expressed. It encodes the 653 amino acid long Rab escort protein-1 (REP1), a regulator of Rab GTPases involved in intracellular vesicular transport. Causative mutations in the CHM gene result in an absent or non-functional REP1 and include small deletions, small insertions, nonsense, frame shift or splice site mutations. Strikingly, missense mutations in REP1 have not been identified. Larger deletions can affect only the entire REP1 locus but also additional genes which often associate with syndromic features. The focus in our lab is to screen for mutations within the REP1 locus but also on chromosomal abnormalities affecting REP1 and its vicinity to understand the biology and syndromic nature of the CHM disease.
Charlotte Poloschek (MD), University Eye Clinic Freiburg, Germany