DELETION IN THE PERIPHERIN RDS GENE IN 2 UNRELATED SARDINIAN FAMILIESWITH AUTOSOMAL-DOMINANT BUTTERFLY-SHAPED MACULAR DYSTROPHY

Background: Autosomal dominant butterfly-shaped macular dystrophy is a ssociated with different mutations of the peripherin/RDS gene. We stud ied the phenotype of two families with a novel large deletion in the p eripherin/RDS gene. Methods: Clinical study, fluorescein angiography, color vision testing, automatic perimetry, electrophysiologic studies, and DNA analysis were performed on all the members of the two familie s. Results: Fundus examination in patients aged 30 to 60 years showed yellow deposits in the macula with a butterfly-shaped pattern. Central choroidal atrophy was present in the older patients only. Macular vis ual function tests (color vision and central visual field) were abnorm al, and electro-oculograms were slightly subnormal in five individuals tested. Electroretinograms and results of dark adaptometry were norma l. Linkage analysis with intragenic polymorphic markers and quantitati ve polymerase chain reaction showed heterozygosity for a large deletio n that removed exons 2 and 3 of the peripherin/ RDS gene in all affect ed members of the two families. Conclusions: This deletion escaped det ection by direct analysis of amplified exons and was identified by int ragenic polymorphic markers analysis, resulting in loss of heterozygos ity from affected parents to affected children, and by quantitative po lymerase chain reaction. The delineation of the molecular defect assoc iated with the disease in these two families allows us to verify the p resence or absence of the disease in clinically unaffected members.