Intrafamilial phenotypic variability in families with RDS mutations: exclusion of ROM1 as a genetic modifier for those with retinitis pigmentosa.
OBJECTIVE
To identify suspected RDS mutations in families in which different people have been identified with either generalised retinal dystrophy or macular dystrophy.


METHODS
Two families with a retinal dystrophy were extensively phenotyped and blood was taken for mutation analysis of the RDS (all) and ROM1 (retinitis pigmentosa patients only) genes.


RESULTS
A novel p.Trp94X mutation in RDS was found in all three affected members of a two-generation family that was associated with retinitis pigmentosa in the son, pattern dystrophy in the daughter and fundus flavimaculatus in the mother. In the second family, the proband with retinitis pigmentosa carried a p.Arg220Trp mutation. The mother, who was unavailable for mutation screening, had adult vitelliform macular dystrophy. No ROM1 mutations were found in those with retinitis pigmentosa in either family.


CONCLUSIONS
Mutations in RDS can be associated with an intrafamilial variation in retinal disease. The phenotypes range from Stargardt-like macular dystrophy to classic retinitis pigmentosa.


CONCLUSIONS
Intrafamilial phenotypic variation may be due to the presence of environmental or genetic modifying factors. The presence of a modifying-sequence change in the coding region of ROM1 for two people with retinitis pigmentosa from two families with intrafamilial variation in RDS mutation phenotype has been excluded in this study.
Leroy
B P
BP
Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
Kailasanathan
A
A
De Laey
J-J
JJ
Black
G C M
GC
Manson
F D C
FD
D000328:Adult; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D010641:Phenotype; D012162:Retinal Degeneration / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics; D059470:Tetraspanins
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C578997:PRPH2 protein, human; D064531:Peripherins; C513106:ROM1 protein, human; D059470:Tetraspanins