A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa.
Mutations within the rhodopsin gene are known to give rise to autosomal dominant retinitis pigmentosa (RP), a common hereditary form of retinal degeneration. We now describe a patient with autosomal recessive RP who is homozygous for a nonsense mutation at codon 249 within exon 4 of the rhodopsin gene. This null mutation, the first gene defect identified in autosomal recessive retinitis pigmentosa, should result in a functionally inactive rhodopsin protein that is missing the sixth and seventh transmembrane domains including the 11-cis-retinal attachment site. We also found a different null mutation carried heterozygously by an unrelated unaffected individual. Heterozygous carriers of either mutation had normal ophthalmologic examinations but their electroretinograms revealed an abnormality in rod photoreceptor function.
Rosenfeld
P J
PJ
Howe Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114.
Cowley
G S
GS
McGee
T L
TL
Sandberg
M A
MA
Berson
E L
EL
Dryja
T P
TP
D000221:Adaptation, Ocular; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003624:Darkness; D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010786:Photoreceptor Cells / Q000503:physiopathology; D017354:Point Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics*
D004247:DNA; D012243:Rhodopsin