Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy

Purpose To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). Methods A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. Results The patients’ median age was 37 years (range, 20–76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to −0.12). A significant decline of BCVA was revealed in patients over 40 years old ( P <0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function ( P <0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) ( P =0.031). Conclusions BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy.