title: Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site.
abstract: Several mutations in the rhodopsin gene in patients affected by autosomal dominant retinitis pigmentosa (ADRP) have recently been described. We report four new rhodopsin mutations in ADRP families, initially identified as hetero-duplexed PCR fragments on hydrolink gels. One is an in-frame 12-bp deletion of codons 68 to 71. The other three are point mutations involving codons 190, 211, and 296. Each alters the amino acid encoded. The codon 190 mutation has been detected in 2 from a panel of 34 ADRP families, while the remaining mutations were seen in single families. This suggests that, consistent with a dominant condition, no single mutation will account for a large fraction of ADRP cases. The base substitution in codon 296 alters the lysine residue that functions as the attachment site for 11-cis-retinal, mutating it to glutamic acid. This mutation occurs in a family with an unusually severe phenotype, resulting in early onset of disease and cataracts in the third or fourth decade of life. This result demonstrates a correlation between the location of the mutation and the severity of phenotype in rhodopsin RP.
authors.affiliation: Molecular Genetics Unit, Department of Human Genetics, Newcastle upon Tyne, United Kingdom.
authors.forename: T J
authors.initials: TJ
authors.lastname: Keen
authors.forename: C F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: D H
authors.initials: DH
authors.lastname: Lester
authors.forename: R
authors.initials: R
authors.lastname: Bashir
authors.forename: M
authors.initials: M
authors.lastname: Jay
authors.forename: A C
authors.initials: AC
authors.lastname: Bird
authors.forename: B
authors.initials: B
authors.lastname: Jay
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003854:Deoxyribonucleotides; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism
chemical_list: D003854:Deoxyribonucleotides; D012243:Rhodopsin