Genetic heterogeneity of butterfly-shaped pigment dystrophy of the fovea.
OBJECTIVE
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.
van Lith-Verhoeven
Janneke J C
JJ
Department of Ophthalmology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Cremers
Frans P M
FP
van den Helm
Bellinda
B
Hoyng
Carel B
CB
Deutman
August F
AF
D000293:Adolescent; D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005584:Fovea Centralis / Q000473:pathology; D005654:Fundus Oculi; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D064531:Peripherins; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000473:pathology; D059470:Tetraspanins
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; C513106:ROM1 protein, human; D059470:Tetraspanins