Genetic heterogeneity in Malattia Leventinese

Malattia Leventinese (ML) is a dominant macular dystrophy characterized by drusen at the posterior pole. ML has been associated with a single mutation (R345W) in the EGF-containing. fibulin-like extracellular matrix protein 1 (EFEMP-1) gene, but also the EFEMP-2 gene, known to share genetic homology with EFEMP-1, is considered a candidate gene for this genetic disorder. We have characterized clinically and genetically seven members of a three-generation family affected by ML. Results showed that five family members were clinically affected but the DNA sequencing failed to reveal the typical R345W mutation. Furthermore, the linkage analysis to EFEMP-1 ( using polymorphic markers D2S337 and D2S2368) and to EFEMP-2 ( using D11S987 and D11S1314 markers) gave negative results. 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.