Molecular genetics of retinitis pigmentosa in Scotland
The name retinitis pigmentosa defines a group of commonly inherited visual disorders, characterised by a progressive loss of vision. The disorder may be inherited in an autosomal dominant, recessive or X-linked recessive manner. Recently, three genes responsible for the autosomal dominant form have been identified: rhodopsin, RDS and ROM-1 on chromosomes 3,6 and 8 respectively. In this project, a panel of Scottish patients with a range of retinal degenerations including typical retinitis pigmentosa, Bardet-Biedl syndrome, Stagardts disease and cone rod dystrophy were screened for the presence of mutations in the rhodopsin and RDS genes using SSCP analysis, followed by direct sequencing to characterise the mutation. Four mutations within the rhodopsin gene and one in the RDS gene were detected and are likely to account for the phenotype in these individuals. Two polymorphisms, unrelated to the disease were also detected. Two of the four rhodopsin mutations and the RDS mutation change an amino acid residue in the corresponding proteins, whilst the third rhodopsin mutation alters the conserved splice site sequence in an intron. The effect of these mutations on the proteins is yet to be realised, but it is possible that they lead to the formation of a protein with impaired function, which in turn alters the biochemical or structural integrity of the rod cell and results in cell death. The fourth rhodopsin mutation occurs in the 3' untranslated region of the gene, but it is unknown whether this has any effect on the transcript or the protein. From the results of this study it is clear that mutations in the rhodopsin and RDS genes are a cause of retinitis pigmentosa, and also that SSCP analysis is an efficient mutation detection method.