title: Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene.
abstract: OBJECTIVE
  To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).
  
  
  METHODS
  All accessible family members were included. They underwent blood sampling and ophthalmological examination including, when possible, full-field ERG and pupillometry. A genome-wide linkage analysis was initiated. Mutation analysis of the RPE65 gene within the linked interval was performed by bi-directional sequencing.
  
  
  RESULTS
  Eleven out of 53 examined members were clinically affected with an EORD. Linkage analysis revealed a maximal lod score of 4.02 (theta=0.1) for the marker D1S207 on 1p31. Mutational screening of the RPE65 gene identified a homozygous R91W mutation co-segregating with the disease in all affected individuals. Eleven homozygotes had nystagmus and acuities ranging from CF to NLP. Two retinal patterns were identified: pattern 1 presented mid-peripheral deep white dot deposits and virtually no clumped pigmentation, whereas pattern 2 showed mid-peripheral pigmented clumps without any white deposits. Homozygotes had no detectable full-field ERG and an abnormal pupillary light reflex. Eleven heterozygotes had normal visual function.
  
  
  CONCLUSIONS
  We identified and characterised an endemic form of early onset rod-cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single RPE65 mutation. Two funduscopic patterns were identified: white dot deposits in earlier stages and clumped pigment in later stages.
authors.affiliation: Hedi Rais Institute of Ophthalmology, Tunis, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: El Matri
authors.forename: Aude
authors.initials: A
authors.lastname: Ambresin
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Aki
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Yvan
authors.initials: Y
authors.lastname: Arsenijevic
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Borruat
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D008040:Genetic Linkage; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000208:ethnology / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D005819:Genetic Markers; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase