Identification of novel CYP4V2 genotypes associated with Bietti crystalline dystrophy and atypical anterior segment phenotypes in Spanish patients.

PURPOSE: To identify the spectrum of disease-causing CYP4V2 variants in Spanish patients with clinically diagnosed Bietti crystalline dystrophy (BCD) over an 8-year period and to analyse the phenotype-genotype correlation of the identified variants.

METHODS: Four unrelated Spanish probands with a clinical diagnosis of BCD were recruited. Ophthalmological examination included visual acuity (VA), slit lamp examination, in vivo corneal confocal microscopy, funduscopy and fluoresceinic angiography. Genomic DNA was obtained from blood samples, and the exons and flanking intron sequences of the CYP4V2 gene were screened by Sanger sequencing. Family members of the patients with mutations in CYP4V2 gene were subsequently studied.

RESULTS: Clinical examination revealed retinal and corneal patterns compatible with BCD in all the participants. We identified a total of six CYP4V2 variants among the four carriers. As far as we know, the variant p.(Trp244Cysfs*33) has not previously been reported. This variant along with p.(Ala204Thr) and p.(Arg443Trp) were combined in three novel pathogenic phenotypes that share the presence of bilateral limbic glistening deposits, severe retinal damage and visual impairment and a fast rate of progression of the disease.

CONCLUSION: To the best of our knowledge, this study represents the largest effort to determine the genetic alterations underlying BCD in Spain to date. Our results show that analysis of CYP4V2 variants is required for a reliable diagnosis of BCD. We report a high prevalence of anterior segment changes in this Spanish BCD cohort, which we consider representative of the Spanish patients.