Comprehensive screening of CYP4V2 in a cohort of Chinese patients with Bietti crystalline dystrophy.

Bietti crystalline dystrophy (BCD) is an autosomal recessive retinal degeneration disorder caused by mutations in CYP4V2. The aim of this study is to describe the genetic and clinical findings in 128 unrelated Chinese patients diagnosed with BCD.Ophthalmological evaluations were performed in all patients. All coding regions of CYP4V2 were amplified and sequenced directly. Real-time quantitative PCR was performed to detect copy number variations. Haplotype analysis was performed in 70 patients with c.802-8_810del17insGC and in 93 normal controls.A total of 28 mutations in CYP4V2, including eight novel mutations, were identified in 125 patients. The most common mutation was c.802-8_810del17insGC, with an allele frequency of 62.6%, followed by p.H331P (8.7%) and c.1091-2A>G (7.5%). A novel large deletion encompassing exon 8 of CYP4V2 was detected. Haplotype analysis revealed four common haplotypes in patients with c.802-8_810del17insGC. A 17.6 kb haplotype CT(delCT)TA(Indel)A was the most common and was observed in 34.5% of the c.802-8_810del17insGC mutant alleles. The patients with mutations in CYP4V2 showed wide intra- and interfamilial variability in clinical severity.The findings expand the mutational spectrum of CYP4V2 and further confirm the c.802-8_810del17insGC mutation was due to a founder effect in a large cohort of Chinese patients.