Severe autosomal dominant retinitis pigmentosa caused by a novel rhodopsin mutation (Ter349Glu). Mutations in brief no. 208. Online.

Abstract

Mutations in the rhodopsin gene are reported to be responsible for approximately 25% of all cases of autosomal dominant Retinitis pigmentosa (adRP). Affected individuals from a large family with an unusually severe form of adRP were screened for mutations in the rhodopsin gene. Direct sequencing of exon 5 revealed a TAA to GAA transversion at nucleotide 5276/codon 349, which was confirmed by Dde1 restriction digest analysis. This change would replace the normal termination codon with a glutamic acid residue (Ter-349-Glu, or X349E). The next predicted termination codon (TAA) lies 153bp downstream at nucleotides 5429 to 5431. Termination of transcription at this point would add an additional 51 amino-acid residues to the carboxy terminus of the rhodopsin molecule. This mutation is unique in producing a mutant rhodopsin in which all of the normal 348 amino-acid residues remain intact. It produces one of the most severe adRP phenotypes ever observed in a family with a rhodopsin mutation. In view of this the Ter-349-Glu mutation is worthy of further investigation to determine how the presence of this particular mutant opsin leads to rod photoreceptor degeneration.