Choroideremia (CHM) is a rare, monogenic X-linked recessive form of hereditary retinal dystrophies that characterized by progressive degeneration of the choroid and retina, ultimately leads to blindness. Choroideremia is caused by a loss of function mutation in the CHM gene which encodes Rab escort protein 1 (REP1), a protein involved in lipid modification of Rab proteins. While the complete mechanism of disease is not fully understood, the lack of a functional protein in the retina results in the degeneration of the choriocapillaris, the retinal pigment epithelium, and the retinal photoreceptor cells. Here, we describe genetic screening of four choroidemia affected men in two unrelated Iranian families.

Genomic DNA was extracted from peripheral blood leukocytes using the standard salting out method and the 15 CHM exons and their flanking regions were amplified by PCR. Candidate variations were screened for segregation in the pedigrees by Sanger sequencing. The in silico bioinformatics tools were used to predict and score the deleterious effects of these nucleotide changes on the protein product.

We identified two different novel mutations including a splice site mutation (NM_000390: IVS8-1 (C>T)) and a nonsense mutation (NM_000390: Gln327*) in CHM. All affected men had hemizygous status for the mutations and their unaffected family members did not have the homozygous or hemizygpus status for them.

To the best of our knowledge, it is the first report on genetics of choroidemia in Iran. Segregation analysis and bioinformatics predictions all support the proposition that the observed CHM mutations are cause of choroideremia in the pedigrees. Both of the mutations are predicted to result in a truncated gene product.