title: Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities.
abstract: Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known to be associated with tritan color-vision deficiency. Here we report a sixth OPN1SW mutation (T190I) and the associated color vision phenotype. S-opsin genotyping and clinical evaluation of color vision were performed on affected and unaffected family members and normal controls. Chromatic contrast was tested at different levels of retinal illuminance. Affected family members were heterozygous for a nucleotide change that substituted the amino acid isoleucine (I) in place of threonine (T) that is normally present at position 190 of the S-opsin. The mutation is in extracellular loop II (EII). The association between making tritan errors and having the T190I mutant S opsin was strong (p>0.0001: Fisher's exact test). The performance of subjects with the T190I mutation was significantly different from that of normal trichromats along the tritan vector under all conditions tested (Mann-Whitney U: p<0.05), but not along the protan or deutan vectors. Individuals with the T190I S-opsin mutation behaved as mild tritans at 12.3-92.3Td, but as tritanopes at 1.2-9.2Td, for both light-adapted and dark-adapted conditions. The results are consistent with the mutant opsin causing abnormal S-cone function.
authors.affiliation: Department of Optometry & Visual Science, Buskerud University College, 3603 Kongsberg, Norway. rigmor.baraas@hibu.no
authors.forename: Rigmor C
authors.initials: RC
authors.lastname: Baraas
authors.forename: Lene A
authors.initials: LA
authors.lastname: Hagen
authors.forename: Elise W
authors.initials: EW
authors.lastname: Dees
authors.forename: Maureen
authors.initials: M
authors.lastname: Neitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055253:Color Vision; D003117:Color Vision Defects / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D005260:Female; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000503:physiopathology; D017299:Rod Opsins / Q000235:genetics* / Q000378:metabolism; D013912:Threonine / Q000235:genetics*; D055815:Young Adult
chemical_list: D017299:Rod Opsins; C095853:short-wavelength opsin; D007532:Isoleucine; D013912:Threonine; D004247:DNA