Background: Choroideremia (CHM) is an X-linked degeneration of the retinal pigment epithelium, photoreceptors, and choroid, which causes nyctalopia and progressive constriction of visual fields leading to blindness. The CHM gene encodes Rab escort protein 1 (REP-1). In this work, we reviewed the phenotypes and genotypes of affected males with the purpose of understanding the functional effects of CHM mutations and their relationship with the phenotypes.
Methods: A retrospective review of 128 affected males was performed analyzing the onset of symptoms, visual acuity, and visual fields with respect to their mutations in the CHM gene.
Results: In rank order, reflecting data from this report, the most common mutations found in the CHM gene were nonsense mutations (41%), exon deletions (37%), and splice sites (14%) associated with a loss of functional protein. In the pool of 106 CHM mutations, we discovered four novel missense mutations (c.238C>T; p.L80F, c.819G>T; p.Q273H, c.1327A>G; p.M443V, and c.1370C>T; p.L457P) predicted to be severe changes affecting protein stability and folding with the effect similar to that of other types of mutations. No significant genotype-phenotype correlation was found with respect to the onset of nyctalopia, the onset of other visual symptoms, visual acuity, or width of visual fields.
Conclusion: There is no evidence to support exclusion of CHM patients from clinical trials based on their genotypes or any potential genotype-phenotype correlations.
Keywords: Choroideremia; Rab escort protein‐1; natural history; retinal dystrophy; visual acuity; visual fields.