Linkage Analysis in Malattia Leventinese, an Autosomal Dominant form of Macular Degeneration

Abstract

Malattia leventinese, an autosomal dominant form of macular degeneration, originates from the Leventine valley in the North of the Ticino Canton of Switzerland and was first published by Vogt and coworkers in 1925 (16). Normally between age 20 and age 30, a few round, brown-yellow, later whitish structures appear in the deeper retinal layers of the posterior pole in both eyes. Later, these spots show confluence and the retina in front of them becomes atrophic. The histological examination discloses round accumulations of eosinophilic hyaline bodies in the pigment epithelium. These structures are connected with the inner layer of Bruch’s membrane and are called “drusen”. Drusen can be divided into degenerative and hereditary drusen. Hereditary (dominant) drusen occur in malattia leventinese, Doyne’s honeycomb dystrophy, Hutchinson-Tay chorioiditis and Holthouse-Batten chorioretinitis. Therefore, Deutman and Jansen (3) proposed the designation “dominant drusen” for all these diseases. The molecular abnormality which underlies the formation of dominant drusen is not known. Since elucidation of the molecular basis of malattia leventinese may also shed light on the pathogenesis of other forms of macular degeneration (e.g. age-related macular degeneration, which - in developed countries - is the most common cause of blindness in older individuals), we have recently initiated genetic linkage studies in a large affected family from the Ticino (Figure 1).