Sorsby fundus dystrophy without a mutation in the TIMP-3 gene

Aims-To examine a large family with an autosomal dominant fundus dystrophy and to investigate whether or not mutations in TIMP-3 gene were involved. Methods-A large family of 58 individuals with an autosomal dominant fundus dystrophy was examined ophthalmologically. A DNA linkage analysis in the 22 q12.1-q13.2 region was performed. The TIMP-3 gene was screened for mutation s in all five exons. Results-In this large family 15 individuals were affected. All other indivi duals were found to be clinically unaffected. Pisciform flecks in the midpe riphery and drusen-like deposits were the most typical ophthalmological fin ding in this family and were encountered from the fifth decade on. Choriore tinal atrophy and neovascularisation with disciform lesions characterised t he disease from the sixth decade on. Linkage analysis using an affected onl y analysis, showed a maximum positive lod score of 3.94 at theta = 0.0 with marker D22S283. No mutations possibly causing Sorsby fundus dystrophy were found in either the exonic sequences, the promotor region, or the 3'UTR. Conchcsion-The family in this pedigree has an autosomal dominant fundus dys trophy, which is most probably Sorsby fundus dystrophy. Although, in the Li nkage analysis, significant positive lod scores were found with the region 22q12.1-q13.2, no causative mutations could be identified in the TIMP-3 gen e.