ABCR gene analysis in familial exudative age-related macular degeneration

PURPOSE. Identification of genetic factors ill the pathogenesis of age-rela ted macular degeneration (MID) is of crucial importance in this common caus e of blindness. Mutations in the Stargardt disease gene (ABCR) were previou sly reported in patients with atrophic forms of AMD. The purpose of this st udy was to analyze familial segregation of ABCR gene mutations in 52 unrela ted multiplex cases of exudative AMD. METHODS. A complete ophthalmological examination including visual acuity me asurement, fundus examination, and fluorescein angiography (FX) was perform ed on each exudative AMD patient. The entire coding sequence of the ABCR ge ne was analyzed using a combination of single-strand conformation polymorph ism and confirmatory sequencing of the exons showing an abnormal pattern of migration. RESULTS. Six heterozygous missense changes were identified. A lack of famil ial segregation was observed in 4 of 6 colon changes (Arg943Gln, Val1433Ile , Pro1948Leu, and Ser2255Ile). Conversely, 2 codon changes cosegregated wit h the disease in 2 small families: Pro940Arg and Leu1970Phe. CONCLUSIONS. The authors believe that segregation of the ABCR gene mutation s with familial cases of AMD has not yet been shown. The analysis of famili al segregation allowed the authors to exclude 4 of 6 codon changes as disea se-causing mutations. Furthermore, it was shown here that the ABCR gene may be rarely involved in exudative AMD, with at best 2 of 52 familial cases ( 4%) related to this susceptibility factor.