Deletion in the Peripherin/RDS Gene in Two Unrelated Sardinian Families with Autosomal Dominant Butterfly-shaped Macular Dystrophy

Background: Autosomal dominant butterfly-shaped macular dystrophy is associated with different mutations of the peripherin/RDS gene. We studied the phenotype of two families with a novel large deletion in the peripherin/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 families.

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 visual function tests (color vision and central visual field) were abnormal, and electro-oculograms were slightly subnormal in five individuals tested. Electroretinograms and results of dark adaptometry were normal. Linkage analysis with intragenic polymorphic markers and quantitative polymerase chain reaction showed heterozygosity for a large deletion that removed exons 2 and 3 of the peripherin/RDS gene in all affected members of two families.

Conclusions: This deletion escaped detection by direct analysis of amplified exons and was identified by intragenic polymorphic markers analysis, resulting in loss of heterozygosity from affected parents to affected children, and by quantitative polymerase chain reaction. The delineation of the molecular defect associated with the disease in these two families allows us to verify the presence or absence of the disease in clinically unaffected members.