title: Characterization of Bietti crystalline dystrophy patients with CYP4V2 mutations.
abstract: OBJECTIVE
  Mutations of the CYP4V2 gene, a novel family member of the cytochrome P450 genes on chromosome 4q35, have recently been identified in patients with Bietti crystalline dystrophy (BCD). The aim of this study was to investigate the spectrum of mutations in this gene in BCD patients from Singapore, and to characterize their phenotype.
  
  
  METHODS
  Nine patients with BCD from six families were recruited into the study. The 11 exons of the CYP4V2 gene were amplified from genomic DNA of patients by polymerase chain reaction and then sequenced. Detailed characterization of the patients' phenotype was performed with fundal photography, visual field testing, fundal fluorescein angiography, and electroretinography (ERG).
  
  
  RESULTS
  Three pathogenic mutations were identified; two mutations, S482X and K386T, were novel and found in three patients. The third mutation, a previously identified 15-bp deletion that included the 3' splice site for exon 7, was found in all nine patients, with six patients carrying the deletion in the homozygous state. Haplotype analysis in patients and controls indicated a founder effect for this deletion mutation in exon 7. Clinical heterogeneity was present in the patients. Compound heterozygotes for the deletion in exon 7 seemed to have more severe disease compared to patients homozygous for the deletion. There was good correlation between clinical stage of disease and ERG changes, but age did not correlate with disease severity.
  
  
  CONCLUSIONS
  This study identified novel mutations in the CYP4V2 gene as a cause of BCD. A high carrier frequency for the 15-bp deletion in exon 7 may exist in the Singapore population. Phenotype characterization showed clinical heterogeneity, and age did not correlate with disease severity.
authors.affiliation: Singapore National Eye Centre.
authors.forename: Kelvin Y C
authors.initials: KY
authors.lastname: Lee
authors.forename: Adrian H C
authors.initials: AH
authors.lastname: Koh
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Victor H K
authors.initials: VH
authors.lastname: Yong
authors.forename: Kit
authors.initials: K
authors.lastname: Yeung
authors.forename: Chong-Lye
authors.initials: CL
authors.lastname: Ang
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D018703:Founder Effect; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion; D012846:Singapore; D014794:Visual Fields
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4