The R345W mutation in EFEMP1 causes malattia leventinese, an autosomal dominant eye disease with pathogenesis similar to an early-onset age-related macular degeneration.
Interestingly, in untagged fibulin-3 studies, one compound, phorbol 12-myristate 13-acetate, reduced R345W fibulin-3 secretion while minimally enhancing WT fibulin-3 secretion, the desired activity and selectivity we sought for ML.
An Arg345Trp (R345W) mutation in epidermal growth factor-containing, fibulin-like extracellular matrix protein 1 (EFEMP1) causes its inefficient secretion and the macular dystrophy malattia leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD).
Mutation screening of the EFEMP1 gene and haplotype analysis were performed in the family, an Indian ML/DHRD family, and a branch of 1 of 39 ML/DHRD families in the United States, in which all affected patients shared a common haplotype.
To investigate retinal microstructure of patients affected with malattia leventinese (MLVT) and mutation in the EFEMP1 gene using high-resolution optical coherence tomography (OCT).
The inherited macular degeneration Doyne honeycomb retinal dystrophy/Malattia Leventinese is thought to be caused by an R345W mutation in the EFEMP1 gene (also called fibulin-3).
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.
Therefore, our results suggest EFEMP-1 or EFEMP-2 genes cannot be excluded as being responsible for ML but other genes have to be considered in the pathogenesis of the disease.
These data present evidence that misfolding and aberrant accumulation of EFEMP1 may cause drusen formation and cellular degeneration and play an important role in the etiology of both ML and AMD.
The Arg345Trp disease-associated allele in the EFEMP1 gene was confirmed in individuals with malattia leventinese and Doyne honeycomb retinal dystrophy.
At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity.