title: Clinical and molecular findings in three Lebanese families with Bietti crystalline dystrophy: report on a novel mutation.
abstract: OBJECTIVE
  Bietti crystalline dystrophy (BCD) is a rare autosomal recessive disorder caused by mutation of the cytochrome P450, family 4, subfamily V, polypeptide 2 (CYP4V2) gene and characterized by retinal pigmentary abnormalities and scattered deposits of crystals in the retina and the marginal cornea. The aim of this study was to investigate the spectrum of mutations in CYP4V2 in Lebanese families, and to characterize the phenotype of patients affected with BCD.
  
  
  METHODS
  Nine patients from three unrelated Lebanese families were clinically and molecularly investigated. Detailed characterization of the patients' phenotype was performed with comprehensive ophthalmic examination, color vision study, fundus photography, visual field testing, retinal fluorescein angiography, electroretinography, and electrooculography. One family was followed for 12 years. The 11 exons of the CYP4V2 gene were sequenced.
  
  
  RESULTS
  Symptoms consisting of night blindness, loss of paracentral visual field, and disturbed color vision were apparent during the third decade of life. Ophthalmoscopy revealed posterior pole crystalline deposits and areas of retinal pigment epithelium atrophy. Fluorescein angiography disclosed geographic areas of the pigment epithelium layer and choriocapillaris atrophy in the posterior pole and fundus periphery. The most striking findings were those of normal electroretinographic responses in some patients and clinical heterogeneity. Two mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and the novel p.V458M (c.1372G>A) mutation in exon 9 in one family.
  
  
  CONCLUSIONS
  These patients are affected with Bietti crystalline dystrophy without corneal involvement. Variation in disease severity and electroretinographic responses suggests that environmental or additional genetic factors influence the course of the retinal disease. The CYP4V2 p.I111T (c.332T>C) mutant allele may be especially prevalent among patients with BCD in Lebanon, resulting from a single founder.
authors.affiliation: Service d’Ophtalmologie, Hôtel-Dieu de France Hospital, Beirut, Lebanon.
authors.forename: Nour Maya N
authors.initials: NM
authors.lastname: Haddad
authors.forename: Naji
authors.initials: N
authors.lastname: Waked
authors.forename: Riad
authors.initials: R
authors.lastname: Bejjani
authors.forename: Ziad
authors.initials: Z
authors.lastname: Khoueir
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.forename: Sandra
authors.initials: S
authors.lastname: Corbani
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D003317:Corneal Dystrophies, Hereditary / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004585:Electrooculography; D004596:Electroretinography; D005091:Exons; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D006801:Humans; D007861:Lebanon; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000201:enzymology / Q000473:pathology*; D012164:Retinal Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4