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

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.