Molecular screening of the CYP4V2 gene in Bietti crystalline dystrophy that is associated with choroidal neovascularization

PURPOSE Bietti crystalline dystrophy (BCD) is an autosomal recessive disease characterized by intraretinal deposits of multiple small crystals, with or without associated crystal deposits in the cornea. The disease is caused by mutation in the cytochrome p450, family 4, subfamily v, polypeptide 2 (CYP4V2) gene. Choroidal neovascularization (CNV) is a rare event in BCD. We report two cases of BCD associated with CNV. CYP4V2 and exon 5 of tissue inhibitor of metalloproteinase 3 (TIMP3) were screened in both cases. A patient with BCD, but without CNV, was also screened to identify pathogenic variations. METHODS Three BCD families of Asian Indian origin were recruited after a comprehensive ophthalmic examination. Genomic DNA was isolated from blood leukocytes, and coding exons and flanking introns of CYP4V2 and exon 5 of TIMP3 were amplified via polymerase chain reaction (PCR) and were sequenced. Family segregation, control screening, and bioinformatics tools were used to assess the pathogenicity of the novel variations. RESULTS Of the three BCD patients, two had parafoveal CNV. The patient with BCD, but without CNV had novel single base-pair duplication (c.1062_1063dupA). This mutation results in a structurally defective and unstable protein with impaired protein function. Four novel benign variations (three in exons and one in an intron) were observed in the cohort. Screening of exon 5 of TIMP3 did not reveal any variation in these families. CONCLUSIONS A novel mutation was found in a patient with BCD but without CNV, while patients with BCD and CNV did not show any pathogenic variation. The modifier role of TIMP3 in the pathogenesis of CNV in BCD was partly ruled out, as no variation was observed in exon 5 of the gene. A larger BCD cohort with CNV needs to be studied and screened to understand the genetics of CNV in BCD.