Purpose: Butterfly-shaped macular dystrophy (BSMD) has so far only been associated with mutations in the peripherin/RDS gene. The initial aim of our study was to investigate the peripherin/RDS gene as the causative gene in a family with BSMD. Subsequently the putative involvement of the ROM-1 gene, 4 genes expressed in cone photoreceptors, all known non-syndromic macular, retinal pigment epithelium and choroidal dystrophy loci, all known Leber congenital amaurosis loci and all known non-syndromic congenital and stationary retinal disease loci was examined.
Methods: Thirteen members from the original family with autosomal dominant BSMD were examined. The protein coding exons of the peripherin/RDS gene were screened for mutations by sequence analysis. Linkage analysis was performed using markers flanking the peripherin/RDS gene to rule out the presence of a heterozygous deletion. Likewise, involvement of the ROM-1 gene, four cone genes, 41 non-syndromic retinal disease loci and one syndromic retinal disease locus was investigated.
Results: Sequence analysis of the peripherin/RDS gene revealed no mutations. In addition, the BSMD phenotype could not be genetically linked to the peripherin/RDS gene, the ROM-1 gene and the four cone genes nor to any of the 42 retinal disease loci.
Conclusions: This study reveals genetic heterogeneity for BSMD by the identification of a BSMD family, which is not associated with a mutation in the peripherin/RDS gene nor with any other known non-syndromic retinal disease gene.