title: Mutation analysis of the ROM1 gene in retinitis pigmentosa.
abstract: To examine the role of ROM1, a homologue of peripherin/RDS, in autosomal dominant retinitis pigmentosa (adRP), we screened 224 adRP and 29 simplex RP probands for ROM1 mutations. Four ROM1 alleles were designated as potentially pathogenic because they were found only in RP patients but not in 50-100 controls nor in 249 other RP probands. The substitutions P60T and T108M were present in a single allele in a subject with typical adRP, and this allele cosegregated with the disease in the small family. The putative null allele L114 [1 bp] was present in an individual with atypical RP but not in three unaffected siblings. This insertion has been previously reported to cause RP only when accompanied by a peripherin/RDS mutation, but no peripherin/RDS mutations were found in any of the four probands reported here. Two substitutions (G75D, R242Q) were present in two other probands with simplex RP. These data suggest that potentially pathogenic ROM1 mutations occur in 1% or less of patients with adRP or simplex RP. The absence of detectable peripherin/RDS mutations in these families suggests either that: (i) mutations in other digenic partners are required for pathogenic ROM1 alleles to cause retinal degeneration; (ii) these ROM1 mutations do not cause RP; or (iii) peripherin/RDS mutations are present but were not identified in these patients.
authors.affiliation: Department of Genetics, Hospital for Sick Children, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Bascom
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001284:Atrophy; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005136:Eye Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D010375:Pedigree; D064531:Peripherins; D010857:Pigment Epithelium of Eye / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D015183:Restriction Mapping; D012162:Retinal Degeneration / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D059470:Tetraspanins
chemical_list: D017931:DNA Primers; 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