Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients

Background: Heterozygous mutations of the bestrophin gene are associated wi th Best macular dystrophy (BMD). The bestrophin gene is specifically expres sed in the retinal pigment epithelium. BMD is a hereditary form of macular degeneration that may develop subretinal neovascularisation similar to the wet type of age-related macular degeneration (AMD). Purpose: To study wheth er mutations of the bestrophin gene occur in non-familial Japanese AMD pati ents. Methods: A total of 85 non-familial AMD patients (average age 67.5 ye ars; 72 male, 14 female) diagnosed by indocyanine green angiography were sc reened. Among them, 69 patients (81%) were classified as having wet type AM D. Genomic DNA was purified from the total blood and used as the template f or polymerase chain reaction (PCR). All the exons of bestrophin gene were a mplified by PCR. Mutation analysis was performed by SSCP using the ABI Pris m 310 Genetic Analyzer (Perkin Elmer). Nucleotide sequence was determined b y direct sequencing of the PCR amplicons. As the control, 105 non-AMD patie nts (average age 62.0 years; 52 male, 53 female) were screened by the same method. Results: Only one AMD patient had a specific polymorphism in exon 2 , but no mutations leading to amino acid substitutions were found. In exon 2 and 3, two further polymorphisms were detected in all AMD patients as wel l as normal controls. Conclusion: No mutations were found in the bestrophin gene in nonfamilial Japanese patients with AMD or in normal controls.