Autosomal dominant retinitis pigmentosa in Norway: a 20-year clinical follow-up study with molecular genetic analysis. Two novel rhodopsin mutations: 1003delG and I179F.
OBJECTIVE
To examine the clinical picture and molecular genetics of 12 Norwegian families with autosomal dominant retinitis pigmentosa (adRP) in order to achieve a genotype-phenotype correlation.


METHODS
In addition to a clinical ophthalmological examination, fundus photography, dark adaptometry and electroretinography were performed. Four genes were analysed: rhodopsin (RHO); retinitis pigmentosa 1 (RP1); retinal degeneration slow/peripherin (RDS/peripherin), and inosine monophosphate dehydrogenase 1 (IMPDH1). Seven of the families had been examined about 20 years previously. A total of 63 patients or first-degree relatives (aged 18-79 years) were examined.


RESULTS
Mutations were found only in the RHO gene. Seven families were given a diagnosis of classical RP. Two of them had novel mutation 1003delG, and one family had the mutation V345M. Four families had pericentral retinal dystrophy (PRD), two families with the mutation A164V and one with novel mutation I179F. One family was given a diagnosis of central and pericentral retinal dystrophy (CPRD), a special type of cone/rod dystrophy, and no mutation was found.


CONCLUSIONS
Six of 12 families had an RHO mutation. The mutation V345M and the novel mutation 1003delG both caused classical RP, the former indicating the most unfavourable prognosis. Two of the families with PRD had the A164V mutation with a favourable prognosis, whereas the novel mutation I179F caused PRD with extremely variable expressivity.
Grøndahl
Jan
J
Department of Medical Genetics, University Hospital, Rikshospitalet, Oslo, Norway.
Riise
Ruth
R
Heiberg
Arvid
A
Leren
Trond
T
Christoffersen
Terje
T
Bragadottir
Ragnheidur
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics; D009664:Norway / Q000453:epidemiology; D010375:Pedigree; D064531:Peripherins; D010641:Phenotype; D010781:Photography; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics*; D014794:Visual Fields
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; C120042:RP1 protein, human; D012243:Rhodopsin; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human