title: Analysis of the EFEMP1 gene in individuals and families with early onset drusen.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic analysis is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases. The Arg345Trp mutation on exon 10 of the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene causes two clinical phenotypes of early onset drusen (Doyne honeycomb retinal dystrophy and Malattia Leventinese), yet does not appear to be involved in other early onset drusen phenotypes or typical AMD. We wished to ascertain the involvement of the EFEMP1 gene in our population of sporadic and familial subjects presenting with early onset drusen and their affected relatives.
  
  
  METHODS
  Individuals presenting with drusen/end-stage maculopathy at 60 years or under were identified from retinal clinics in Melbourne. All available first- and second-degree relatives were also examined. In all, 116 ethnically matched controls were collected from the same community for comparison.
  
  
  RESULTS
  Single stranded conformational polymorphism (SSCP) analysis and subsequent sequencing revealed four previously described and three novel sequence variations. Most occurred at similar frequencies in the case and control populations and were not thought to be disease associated.
  
  
  CONCLUSIONS
  The term early onset drusen encompasses a wide range of phenotypes and our findings indicate that it is likely that more than one gene is involved in its causation. It is essential that these clinical phenotypes are well described and categorised to allow greater possibility of success in the search for other disease genes.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, 3002 Melbourne, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Narendran
authors.forename: R H
authors.initials: RH
authors.lastname: Guymer
authors.forename: M
authors.initials: M
authors.lastname: Cain
authors.forename: P N
authors.initials: PN
authors.lastname: Baird
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D015593:Retinal Drusen / Q000175:diagnosis / Q000235:genetics
chemical_list: C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins