title: Genotype phenotype analysis of Bietti's crystalline dystrophy in patients with CYP4V2 mutations.
abstract: OBJECTIVE
  To evaluate the genotypic and phenotypic correlations of Bietti's crystalline dystrophy (BCD) in patients with the CYP4V2 gene by mutation screening and clinical and electrophysiological assessment.
  
  
  METHODS
  Eighteen Chinese patients in 13 families with BCD were recruited for full ophthalmic examinations, optical coherence tomography (OCT), and visual electrophysiological tests, including electrooculography (EOG), full-field electroretinography (ERG), and multifocal electroretinography (mfERG). Peripheral venous blood was obtained from all index patients and their family members for genomic DNA extraction and CYP4V2 sequence screening by direct sequencing.
  
  
  RESULTS
  All 18 patients with BCD had mutations in the CYP4V2 gene: five were novel (Y219H, W244X, D324V, P396L, and R400C) and four had been reported. A common mutation occurred at the splice site IVS6-8del17bp/insGC of 12 patients, four being homozygous. OCT showed the presence of intraretinal crystals in all patients. Patients with more severe thinning of the retina had worse visual acuity, and there was moderate correlation between the OCT central foveal thickness and visual acuity (Spearman rho = 0.46, P = 0.005). Patients with splice site mutations (i.e., homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G) had lower EOG Arden index (P = 0.014) and were more likely to have a nonrecordable scotopic full-field ERG (P = 0.003) and nonrecordable 30-Hz flicker ERG (P = 0.043).
  
  
  CONCLUSIONS
  BCD patients with homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G mutations appeared to have more severe disease phenotype based on electrophysiological testing. The level of visual loss in BCD is related to the severity of retinal thinning.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong. tyylai@cuhk.edu.hk
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Ng
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Gary H F
authors.initials: GH
authors.lastname: Yam
authors.forename: Jasmine W S
authors.initials: JW
authors.lastname: Ngai
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Chan
authors.forename: David T L
authors.initials: DT
authors.lastname: Liu
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4