Purpose To report the genetic analysis of an Iranian Bietti crystalline dystrophy (BCD)-affected family, and to review previously reported mutations in the gene and assess the distribution of affected amino acids in the encoded protein. Methods The eleven exons of CYP4V2 were sequenced in the DNA of the proband of the Iranian BCD family. The putative disease-causing variation was screened in all affected and non-affected members. BCD causing CYP4V2 mutations previously reported in the literature were compiled, and positions of amino acids affected by nonsense and missense mutations were mapped onto the primary structure of the CYP4V2 protein. Results C.1219G > T in CYP4V2 that causes p.Glu407* was identified as cause of BCD in the Iranian family. The mutation segregated with disease status. Clinical presentations were similar among affected members, except that one patient presented with retinal macular hole. Twelve nonsense and 47 missense mutations in CYP4V2 were compiled. Inspection of distribution of amino acids affected by the mutations suggested non-random distribution and clustering of affected amino acids in nine regions of the protein, including regions that contain the heme binding site, the metal binding site, and a region between these binding sites. The most C-terminus proximal nonsense mutation affected position 482. Conclusions This study presents results of the genetic analysis of an Iranian BCD family. Protein regions affected by mutations within the nine mutation clusters include regions well conserved among orthologous proteins and human CYP4 proteins, some of which are associated with known functions. The findings may serve to identify reasonable candidate gene region targets for gene editing therapy approaches.

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