title: Novel mutations in the CYP4V2 gene associated with Bietti crystalline corneoretinal dystrophy.
abstract: OBJECTIVE
  Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive disorder of retinal degeneration characterized by small glittering crystals in the corneal limbus, posterior pole of the eye, and circulating lymphocytes. Recently mutations in a new gene CYP4V2, encoding a protein belonging to a novel member of the cytochrome P450 family, have been identified as the cause of BCD. To further characterize the role of CYP4V2 in BCD, mutation screening has been undertaken in a cohort of affected patients with BCD from China.
  
  
  METHODS
  Eight unrelated families, including 14 patients and 18 unaffected relatives, and 10 sporadic patients were examined clinically. Fifty normal Chinese individuals served as control subjects. Genomic DNA was extracted from venous blood of all participants. The coding region (including the intron-exon boundary) of CYP4V2 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed using direct sequencing and single strand conformation polymorphism (SSCP).
  
  
  RESULTS
  Fundus examination revealed clinical features of BCD with many small, yellowish-sparkling crystals at the posterior pole of the fundus. Sequencing of CYP4V2 identified nine (5 missense, 1 nonsense, 2 deletion, and 1 point A-->G transversion in the splice acceptor site) mutations in 8 families and 9 independent patients. Five of these mutations are novel.
  
  
  CONCLUSIONS
  Our finding expands the spectrum of CYP4V2 mutations causing BCD, and further confirms the role of CYP4V2 in the pathogenesis of BCD.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China. shanminghua@hotmail.com
authors.forename: Minghua
authors.initials: M
authors.lastname: Shan
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.forename: Xueqin
authors.initials: X
authors.lastname: Zhao
authors.forename: Jingzhao
authors.initials: J
authors.lastname: Wang
authors.forename: Genlin
authors.initials: G
authors.lastname: Li
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4