title: Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy.
abstract: BACKGROUND
  Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessively inherited disorder characterised by tiny yellowish glittering retinal crystals, choroidal sclerosis, and crystals in the peripheral cornea, associated with progressive night blindness. CYP4V2, encoding a member of cytochrome p450 (CYP450) protein family, was recently identified as the causative gene.
  
  
  METHODS
  We recruited 11 unrelated patients with BCD and characteristic clinical features; eight of Japanese, two of Middle Eastern, and one of Chinese ancestry. Genomic DNA was extracted from peripheral blood leucocytes, and all 11 exons and the flanking intron splice sites of the CYP4V2 gene were amplified and sequenced. A complete ophthalmological examination was performed.
  
  
  RESULTS
  We found recessive mutations in the CYP4V2 gene in all of the 11 patients. Two novel mutations, L173W and Q450X, were identified in a Japanese patient and two unrelated patients from Middle Eastern countries, respectively. Each patient was a homozygote. A previously reported mutation IVS6-8_810delinsGC was identified in seven unrelated Japanese patients and the Chinese patient with BCD. All patients with BCD shared a characteristic fundus appearance with numerous intraretinal crystal deposits and atrophy of the retinal pigment epithelium. However, the clinical findings, including elecroretinograph recordings, indicated that there was considerable variation in the degree of visual dysfunction even among patients of similar ages carrying the same mutation.
  
  
  CONCLUSIONS
  Defects in CYP4V2 are the main cause of BCD. The IVS6-8_810delinsGC mutant allele may be especially prevalent among patients with BCD in East Asian countries, resulting from a single founder. Variation of disease severity suggests that environmental or additional genetic factors influence the course of the retinal disease.
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: K M
authors.initials: KM
authors.lastname: Nishiguchi
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002681:China; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008877:Middle East; D009154:Mutation; D010375:Pedigree; D010857:Pigment Epithelium of Eye / Q000473:pathology; D016415:Sequence Alignment
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4