Analysis of the Arg345Trp disease-associated allele of the EFEMP1 gene in individuals with early onset drusen or familial age-related macular degeneration

Background: A single base change within the EFEMP1 gene has been associated with malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly inherited macular diseases with early onset drusen. The aim of this study was to determine whether the same disease allele was also associated with other forms of early onset drusen or familial cases of age‐related macular degeneration. Methods: Thirteen index cases of early onset drusen together with 15 other family members were examined. In addition, 54 familial cases of age‐related macular degeneration were examined. Blood was taken for DNA analysis and screened for the Arg345Trp disease‐associated allele of the EFEMP1 gene. Twenty‐four cases of malattia leventinese or Doyne honeycomb retinal dystrophy were also screened as positive controls. Another 150 ethnicity‐ and age‐matched individuals acted as controls. Results: The Arg345Trp disease‐associated allele in the EFEMP1 gene was confirmed in individuals with malattia leventinese and Doyne honeycomb retinal dystrophy. However, involvement of this allele was not evident in either early onset drusen or familial age‐related macular degeneration. Conclusions: The Arg345Trp disease‐associated allele of the EFEMP1 gene does not appear to be associated with cases of early onset drusen that fall outside the diagnosis of malattia leventinese or Doyne honeycomb retinal dys­trophy, nor does it appear to play a role in familial age‐related macular degeneration. These findings do not exclude the involvement of other alleles of the EFEMP1 gene in either phenotype. The genetic mechanisms involved in the hetero­geneous group of early onset drusen remain to be elucidated but should lead to insights into the genetic causes of macular diseases.