A Novel Missense Mutation in the S Cone Photopigment in a Male Who Made Tritan Errors on the Neitz Test of Color Vision

Abstract

Abstract: : Purpose: In an ongoing effort to identify new mutations that underlie inherited color vision deficiency, we screened 425 medical students for defects using the Neitz Test of Color Vision. One (#4041) student was unique in that he made errors on the two tritan symbols but made no other errors. To test the hypothesis that subject #4041 has a mutation in his S cone photopigment gene, his S cone photopigment genes were sequenced and compared to the sequence of the S opsin genes from 107 subjects with normal color vision. Three amino acid substitutions in the S opsin gene have previously been associated with tritanopia, which is a rare autosomal dominant color vision defect that is estimated to affect 1 in 10,000 people. Methods: The S cone photopigment gene from subject #4041 was amplified with the polymerase chain reaction, and the coding region was sequenced. A new mutation was found. The S cone opsin genes in 107 individuals with normal color vision were screened for this mutation using the Transgenomic WAVE-MD denaturing high performance liquid chromatography (dHPLC) system. Results: Subject #4041 was heterozygous for a single nucleotide change in exon 1 of his S cone opsin genes. The mutation leads to a substitution of proline for leucine at amino acid position 56 of the S opsin. This mutation was not detected by dHPLC in 107 subjects with normal color vision. Conclusions: Evidence indicating that substituting proline for leucine at amino acid position 56 of the S cone opsin causes a tritan defect include (i) all known amino acid substitutions in S opsin cause tritanopia, (ii) a proline at position 56 is expected to introduce a bend in helix I that is likely to disrupt photopigment function, (iii) alignment of all members of the rhodopsin family of G-protein coupled receptors in the GPCR database reveal that this amino acid position is highly conserved, with 76% of the 137 opsins in the database having leucine, and 24% having either valine, isoleucine or methionine; no member of this family has proline at this position, (iv) subject #4041 made only tritan errors on the Neitz Test of Color Vision, and (v) the substitution was not found in 107 individuals with normal color vision.

Keywords: color pigments and opsins • color vision • gene/expression