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Red-Green Color Vision Defects

Includes: Red-Green Color Blindness

, PhD and , MD.

Author Information
, PhD
Research Professor, Medicine and Genome Sciences
University of Washington
Seattle, Washington
, MD
Professor Emeritus (Active), Medicine and Genome Sciences
University of Washington
Seattle, Washington

Initial Posting: ; Last Update: September 29, 2011.

Summary

Disease characteristics. Hereditary red-green color vision defects manifest mostly in males; the condition is not accompanied by ophthalmologic or other associated clinical abnormalities. Most individuals with protanomalous and deuteranomalous color vision defects (i.e., they are anomalous trichromats) have no problems in naming colors; some males with mildly defective red-green color vision may not be aware of it until they are tested. Individuals with dichromatic color vision defects (i.e., they are dichromats) are more proficient in deciphering texture camouflaged by color than observers with normal red-green color vision. Among individuals of northern European origin, about 8% of males and 0.5% of females have red-green color vision defects; these defects are less frequent among males of African (3%-4%) or Asian (3%) origin.

Diagnosis/testing. Clinical chart tests widely used to detect red-green color vision defects include Ishihara plates and the American Optical HRR pseudoisochromatic plates. Definitive classification of the color vision defects known as protanopia, deuteranopia, protanomaly, and deuteranomaly requires use of the anomaloscope, which involves color matching. The two genes in which mutation is associated with red-green color vision defects are OPN1LW (opsin 1 long wave), encoding the red pigment and OPN1MW (opsin 1 middle wave), encoding the green pigments. Approximately 75% of all red-green color vision defects (100% of protans and about 65% of deutans) can be diagnosed by molecular genetic testing for these genes.

Management. Treatment of manifestations: Tinted contact lenses with individually preferred filters may improve color discrimination. Color presentations that are not confusing to observers with color vision defects can be used in educational settings.

Prevention of secondary complications: Detection of severe red-green color vision defects at high school age should be communicated to parents and affected boys since this finding may be relevant for certain occupational choices.

Genetic counseling. Red-green color vision defects are inherited in an X-linked recessive manner. Because the mother of a proband is an obligate carrier of the mutation, the chance of transmitting the mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers. Affected males transmit the mutation to all of their daughters, who will be carriers, and to none of their sons. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible through laboratories offering either testing for the gene of interest or custom testing.

Diagnosis

Clinical Diagnosis

Normal trichromatic color vision. The human retina contains two types of photoreceptors:

  • Rods for vision in dim light
  • Cones for vision in daylight and for color vision

Note: Each photoreceptor cell contains a single type of photopigment that is composed of a protein moiety (opsin) to which the chromophore 11-cis retinal is covalently bound.

Normal human color vision is trichromatic and is based on the three classes of cones (Figure 1) that are maximally sensitive to light at:

Figure 1A

Figure

Figure 1A. The light absorption spectra of the three classes of cone photopigments of humans with normal trichromatic color vision. Relative light absorption is plotted against wavelength in nanometers (nm); the wavelength of maximal absorption of the (more...)

  • ~420 nm: blue cones or "S" cones for short wavelength
  • ~530 nm: green cones or "M" cones for middle wavelength
  • ~560 nm: red cones or "L" cones for long wavelength

Note: (1) Red and green photopigments differ in the wavelength of maximal absorption by approximately 30 nm [Sharpe et al 1999, Motulsky & Deeb 2001]. (2) Both red and green cones are needed to perceive the colors in the red-green region of the spectrum because perception of these colors depends on comparison between the signal outputs of the red and the green cones in the retina and brain. (3) The three classes of cone photoreceptors allow perception of about one million colors in the visible spectrum. (4) Considerable individual variation exists in the total number of red and green cone photoreceptors in the human retina. The red-to-green cone ratio ranges between 1 red : 2 green to 8 red : 1 green, with a median of 4 red : 1 green [Yamaguchi et al 1997, Carroll et al 2002]. Differences in the red-to-green cone ratio do not appear to affect color vision as tested in the laboratory, but could have some effects in natural settings.

Defective red-green color vision. The common red-green color vision defects are divided into four subclasses based on severity and the type of missing or anomalous red and green cone photoreceptors (reviewed in Sharpe et al [1999], Motulsky & Deeb [2001], Neitz & Neitz [2004]). The decreasing order of severity of the various color vision defects is protanopia, deuteranopia, protanomaly, and deuteranomaly.

  • Severe red-green color vision defects (i.e., dichromatic color vision) are usually mediated by two types of photoreceptors:
    • Protanopia. Blue and green cones only; no functional red cones (~1% of white males) (Figure 2A)
    • Deuteranopia. Blue and red cones only; no functional green cones (~1% of white males) (Figure 2B)
  • Milder red-green color vision defects (i.e., anomalous trichromacy) are mediated by three types of photoreceptors:
    • Protanomaly. Normal blue and green cones plus anomalous green-like cones (~1% of white males) (Figure 2C)
    • Deuteranomaly. Normal blue and red cones plus anomalous red-like cones (~5% of white males) (Figure 2D)
Figure 2

Figure

Figure 2. Absorption spectra of retinal cone photoreceptors of males with defective color vision

A. The absorption spectra of a male with protanopia (blue [B] and green [G] cones only)

B. The absorption spectra of a male (more...)

Note: "Protan" refers to both protanopia and protanomaly. "Deutan" refers to both deuteranopia and deuteranomaly.

Individuals with dichromatic color vision (dichromats) have more abnormal color vision than individuals with anomalous trichromatic color vision.

  • Most dichromats perceive the visible spectrum as lacking red, orange, green, blue, and cyan. As a result they have difficulty selecting colored articles, materials, and foods. Colors of the red family may appear black to protanopes.
  • Anomalous trichromats perceive colors in the green-red region, but color saturation is weakened. Severity of color discrimination deficits varies widely. Some deuteranomalous persons are not aware of their color vision deficits, while others have color vision deficits that are close to those of dichromats.

Simulation of how protanopes, deuteranopes, and tritanopes see colored images can be visualized at www.vischeck.com and jfly.iam.u-tokyo.ac.jp.

Testing

Phenotypic Color Vision Testing

Ishihara plates and American Optical HRR Pseudoisochromatic plates. These are widely used clinical chart tests to detect red-green color vision defects. Sets of variable color dots are printed as numbers (Ishihara) or symbols (HRR) that need to be read or traced by the test subject (Figure 3). Individuals with defective red-green color vision miss certain numbers or symbols or misread them [Birch 2001]. Color vision charts are available in the offices of most ophthalmologists and optometrists. Color chart testing may be indicated to assess color vision in the evaluation of certain retinal diseases or in acquired color vision defects.

Figure 3

Figure

Figure 3. The Ishihara test for the common red-green color vision defects. Shown are six of the Ishihara (pseudoisochromatic) plates that are commonly used for screening observers (images from www.toledo-bend.com/colorblind/Ishihara.asp). A person with (more...)

For testing children between ages four and seven years for color vision defects, certain discriminatory Ishihara plates have been selected and a special Ishihara test has been constructed based on a small number of test plates, using shapes, pictures, and pathways instead of numbers [Birch 2001].

Lantern tests. The Farnsworth Lantern (FALANT) test is a color-naming test used by US federal agencies (not used clinically). Color pairs (including red, green, and white) are shown and the pass/fail level is based on the number of color-naming errors. All dichromats and 75% of anomalous trichromats fail this test. The distribution of pass and fail grades is continuous without bimodality.

Anomaloscope. A more sophisticated instrument is the anomaloscope, which requires color matching. The person views a pure yellow light on one half of a screen while the other half projects a mixture of red and green lights. The brightness of the yellow light and the proportion of the green and red lights are adjusted by the person who is tested until both hemi-fields appear identical in color and brightness. The range and midpoint of accepted matches of the proportion of green and red light are recorded.

  • Individuals with normal color vision accept matches in a narrow range.
  • Individuals with severe color vision defects (protanopia and deuteranopia) accept all matches.
  • Individuals with milder red-green color vision defects (protanomaly and deuteranomaly) accept characteristic wide match ranges.

Definitive classification of protanopia, deuteranopia, protanomaly, and deuteranomaly requires use of the anomaloscope. Anomaloscopy is generally less available than color vision charts and is usually not required for clinical purposes.

Molecular Genetic Testing

Genes. The two genes in which mutations cause red-green color vision defects are:

  • OPN1LW (opsin 1 long wave) encoding the red pigment;
  • OPN1MW (opsin 1 middle wave) encoding the green pigments.

These two genes are arranged in a head-to-tail cluster (or “array”) composed of one red pigment gene followed by one or more green pigment genes [Nathans et al 1986, Nathans 1989] (Figure 4). However, only two genes (i.e., the single red pigment gene and the adjacent green pigment gene) are expressed in retinal photoreceptors and, therefore, contribute to the color vision phenotype. The pigment genes in the third or more distal positions of the cluster, whether normal or abnormal, are not expressed.

Figure 4

Figure

Figure 4. Variation in the red and green pigment gene clusters observed in individuals with normal color vision. The gene cluster on the X-chromosome consists of one red pigment gene 5' of one or more green pigment genes. The number of green pigment genes (more...)

Differences at codons 180, 277, and 285 account for the majority of the 30-nm difference in λmax between the normal red and green pigments (Figure 4).

The juxtaposition and high degree of sequence homology between the repeat units of the red and green pigment genes, including introns and intergenic regions, predisposes these genes to relatively frequent illegitimate or unequal crossing-over events. These events either cause changes in gene number (including deletions) because of unequal recombination in the intergenic region (Figure 5A) or formation of a variety of red-green hybrid genes as a result of intragenic recombination (Figure 5B). These hybrid genes encode chimeric pigments that vary in wavelength of maximal absorption (λmax). The exchange of exon 5 converts a red pigment to a green-like pigment or a green pigment to a red-like pigment. These chimeric pigments have significantly widened variation in color vision phenotype.

Figure 5

Figure

Figure 5. Changes in gene number and formation of red-green hybrid genes.
Intergenic recombination results in changes in the number of green pigment genes, including their deletion, as observed in deuteranopes. Squares represent the six exons (more...)

Research testing

Mutation scanning to detect gene clusters associated with red-green color vision defects. Approximately 75% of all red-green color vision defects (100% of protans and about 65% of deutans) can be diagnosed by such molecular methods [Deeb et al 1992, Jagla et al 2003, Ueyama et al 2006].

Protan color vision defects. The first gene in the cluster together with the promoter can be amplified using a forward primer upstream of and specific for the red pigment gene and a gene-specific reverse primer in exon 5 [Kainz et al 1998, Deeb et al 2000]. The reverse primer may be one that matches red or green exon 5 sequences.

In males with protan color vision defects, the first gene in the cluster is a red-green hybrid gene with various points of fusion, all of which include a green exon 5 (see Figure 6, clusters 1-3), and would only be amplified using a green-specific exon 5 reverse primer. Using gene-specific exon 5 reverse primers, one can easily determine whether a red gene (present in non-protan males) or a red-green hybrid gene (present in a deutan male) occupies the first position in the cluster. This represents a rapid diagnostic test for protan color vision defects in males and for detection of female carriers of protan alleles (amplify with both red and green exon 5 reverse primers) [Kainz et al 1998, Deeb et al 2000].

Figure 6

Figure

Figure 6. Typical gene clusters associated with red-green color vision defects. The common red-green color vision defects are caused either by deletions of the gene (e.g., B6) or by formation of red/green hybrid genes (e.g., A1, A2, A3, B4, B5). Homologous (more...)

Note: Males with deutan color vision defects cannot be identified by this method because (like individuals with normal color vision) they have a normal red pigment gene in the first position of the cluster.

Deutan color vision defects

  • Males with deuteranomaly caused by green-red hybrid genes. The gene clusters of most males with deuteranomaly are composed of one normal red gene followed by one green-red hybrid gene and one or more normal green pigment genes (Figure 6, clusters 4 and 5). However, the green-red hybrid gene must occupy the second position in the cluster in order to be expressed and hence cause red-green color vision deficiency [Hayashi et al 1999].

    In general, green-red hybrid genes with fusion points in intron 4 can be easily detected by PCR amplification using a green-specific forward primer in exon 4 and a red-specific reverse primer in exon 5 [Deeb et al 2000]. Other green-red hybrid genes with fusions in other introns require more detailed analysis by either sequencing or by single-strand conformation polymorphism (SSCP) analysis [Deeb et al 2000].

    Note: (1) To determine whether the green-red hybrid gene occupies the second position in the cluster, the cluster must contain no more than a total number of three genes [Hayashi et al 1999] (e.g., a single red gene, one normal green gene, and a green-red hybrid gene). (2) The presence of more than two green or green-like genes is relatively common.
  • Males with deuteranopia caused by a single red pigment gene. Such males can be identified by PCR amplification using gene-specific exon 4 forward and exon 5 reverse primers (Figure 6, cluster 6) [Deeb et al 2000]. In such individuals, amplification is generally possible with red-specific primers.

Sequence analysis detects point mutations in the red and green pigment genes that cause about 1%-2% of red-green color vision defects.

Table 1. Summary of Molecular Genetic Testing Used in Red-Green Color Vision Defects

Test MethodMutations Detected Mutation Detection Frequency 1 in Individuals with Red-Green Color Vision Defects
Protan 2Deutan 3
Mutation scanning Deletions, green-red hybrid genes100% ~65%
Sequence analysis Missense mutations of OPN1MW or OPN1LW 41%-2%

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. "Protan" refers to both protanopia and protanomaly.

3. "Deutan" refers to both deuteranopia and deuteranomaly.

4. Opsin 1 long wave and opsin 1 middle wave genes encoding the red and green pigments, respectively

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis in a proband. The diagnosis is based on clinical findings (see Clinical Diagnosis).

Clinical Description

Natural History

Hereditary red-green color vision defects are manifest in early infancy. Once fully expressed, the condition remains stable throughout life. Affected persons are predominantly males. The condition is not accompanied by ophthalmologic abnormalities and the retinal fundus appears normal. There are no other associated clinical abnormalities. For further information see Suggested Reading.

Most persons with protanomalous and deuteranomalous color vision defects (i.e., anomalous trichromats) have no problems in naming colors. Some males with mildly defective red-green color vision may not be aware of it until they are tested. They are said to be able to decipher camouflage better than persons without color vision defects [Judd 1943].

Individuals with dichromatic color vision defects (i.e., dichromats) are more proficient in deciphering texture that is camouflaged by color than observers with normal red-green color vision [Morgan et al 1992].

Persons with red-green color vision defects are generally excluded from a variety of industrial, marine, air, rail, and military occupations that require the ability to distinguish red and green colors. Although persons with mild red-green color vision defects may be able to discriminate color on simple practical tasks, such as the FALANT lantern test, the stricter requirements of color discrimination on color chart testing are often utilized for occupational assignments, particularly those related to public safety.

Heterozygotes. Since red-green color vision defects are inherited in an X-linked recessive manner, only rare female homozygotes and occasional female heterozygotes with skewed X-chromosome inactivation (see Penetrance) have X-linked red-green color vision defects.

Genotype-Phenotype Correlations

Genotype-phenotype correlations for red-green color vision defects are discussed in Diagnosis.

Among females and males considered to have normal color vision, a subtle variation in color perception in the red-green region of the visible spectrum has been observed using color matching tests [Waaler 1968, Alpern 1979, Neitz & Jacobs 1986]. This variation is caused by the presence of a common polymorphism at amino acid position 180 of the red pigment.

Higher sensitivity to red light perception among males with normal color vision was strongly correlated with the presence of Ser at position 180 [Winderickx et al 1992a]. A pigment encoded by the allele with Ala at 180 has an approximately 5-nm shorter wavelength of maximal absorption (λmax) than that encoded by the Ser allele [Merbs & Nathans 1992, Asenjo et al 1994].

In the white population, 62% of males have Ser and 38% have Ala at amino acid position 180 of the red pigment [Winderickx et al 1992a]. This common polymorphism explains the subtle difference in red color perception between individuals that is not associated with a red-green color vision defect.

Penetrance

Males with X-linked red-green color vision defects express the defect when appropriately tested; however, a significant fraction (15%-30%) of deuteranomalous trichromats who constitute 5% of the entire male white population may not be aware of their color vision abnormality until it is detected by a screening plate test.

Female carriers usually have no red-green color vision defects. Occasionally, skewed inactivation of the X chromosome with the normal red and green pigment genes in females who carry a mutation in the red or green pigment gene of the other X chromosome allows full expression of the abnormal gene and causes defective red-green color vision. Skewed X-chromosome inactivation is more common in identical female twin pairs. In pairs who are heterozygous for a genetic abnormality associated with red-green color vision defects [Jorgensen et al 1992], one twin inactivates completely her X chromosome with the normal red-green genes while her co-twin inactivates the X chromosome with the red-green gene rearrangement associated with defective red-green color vision. Thus, one twin has a red-green color vision defect while the other twin has normal color vision.

Females homozygous for identical gene rearrangements associated with red-green color vision defects on both of their two X chromosomes and males who have a red-green color vision defect are similarly affected.

Prevalence

Red-green color vision defects are common.

  • Among individuals of northern European descent, about 8% of males and 0.5% of females have red-green color vision defects, and 15% of females are heterozygotes (carriers).
  • Red-green color vision defects are significantly less frequent among males of African (3%-4%) or Asian (3%) ancestry [Motulsky & Deeb 2001], largely because of the presence of more deuteranomalous individuals among individuals of northern European descent (5%).

Differential Diagnosis

Color vision defects are grouped into four major classes: the common red-green defects, blue cone monochromacy, tritanopia, and achromatopsia (Figure 7).

Figure 7

Figure

Figure 7. Classes of color vision defects. Circles represent blue (B), green (G) and red (R)-sensitive cones in the retinae of males with normal and defective color vision. Cones that are labeled G' and R' are those that contain anomalous green-like and (more...)

Blue cone monochromacy. See Genetically Related Disorders

Tritan defects are caused by missense mutation of the gene encoding the S (or blue) retinal cone pigment on chromosome 7 [Weitz et al 1992a, Weitz et al 1992b]. Unlike the X-linked red-green color vision defects, tritan color vision defects are found in males and females equally and are transmitted in an autosomal dominant manner with incomplete penetrance. Color discrimination defects in the short-wave region of the spectrum (blue-yellow) are observed. The American Optical HRR pseudoisochromatic plates detect tritan defects while the Ishihara plates do not.

Achromatopsia (rod monochromatism, total color blindness) is characterized by reduced visual acuity, pendular nystagmus, sensitivity to light (photophobia), eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes. Best visual acuity is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time. Mutations in CNGA3, CNGB3, GNAT2, and PDE6C are causative. Inheritance is autosomal recessive.

Acquired color vision defects may be associated with various eye diseases (e.g., macular dystrophy) and optic nerve or brain diseases that usually manifest with other ophthalmic or clinical findings and require consultation with expert ophthalmologists and neurologists [Birch 2001]. Such acquired defects may be difficult to classify and frequently may exhibit reduced visual acuity and/or visual field defects. Males and females are equally affected. In contrast to hereditary red-green color vision defects, which are always bilateral, acquired color blindness can be monocular. Because hereditary red-green color vision defects occur in 8% of males, incidental occurrence of such red-green color vision defects may be found unrelated to the associated ocular disease under study.

Drugs such as chloroquine and digitalis may occasionally cause acquired bilateral color vision defects that are rarely confused with the common hereditary red-green color vision defects.

Certain environmental chemicals cause human color vision abnormalities. For example, color vision abnormalities were associated with occupational exposure to mercury vapor even several years post intoxication [Feitosa-Santana et al 2007, Rodrigues et al 2007, Feitosa-Santana et al 2008].

In addition, exposure of car-painting workers to a mixture of organic solvents was significantly associated with color vision impairment [Attarchi et al 2010].

Occupational exposure to styrene was found to be associated with visual contrast sensitivity but not with color vision impairment [Seeber et al 2009].

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with red-green color vision defects, the following evaluations are recommended:

Treatment of Manifestations

Tinted contact lenses (Chromagen™) (Cantor and Nissel) are available. These contact lenses require the affected individual to select a preferred filter from a group of colors ranging across the spectrum. The filters may minimally improve color discrimination. Chromagen™ contact lenses are not FDA approved but have FDA marketing clearance for use in red-green color deficiencies.

A Web site, jfly.iam.u-tokyo.ac.jp, includes instructions on how to prepare color presentations that are not confusing to observers with color vision defects.

Prevention of Secondary Complications

The detection of severe red-green vision defects at high school age should be communicated to parents and affected boys since this finding may be relevant for certain occupational choices [Birch 2001].

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Potential gene therapy for color vision-deficient humans

  • Protanopia and deuteranopia. The improvement of red-green color blindness by gene therapy was explored in dichromatic adult squirrel monkeys (Saimiri sciureus) that were missing the L-opsin gene. Subretinal injection of a recombinant adeno-associated virus expressing the L-opsin under the control of L-opsin promoter and LCR was performed. The introduction of a third randomly positioned cone photoreceptor into the retina resulted in trichromatic color vision behavior, suggesting that the originally suggested developmental neuronal connections are not required to acquire extra color discrimination capacity in adults. This provides the potential for similar gene therapy to improve color vision in humans in the foreseeable future [Mancuso et al 2009].
  • Achromatopsia. Although the cones in human achromatopsia are nonfunctional, they do not disintegrate and are good targets for gene therapy. Gene therapy of mouse and dog models of achromatopsia with nonfunctional cone photoreceptors was shown to rescue cone function after transduction of cones by subretinal injection with a recombinant adeno-associated virus (AAV) that expressed the normal genes in the green (but not blue) cones [Komáromy et al 2010, Michalakis et al 2010].
  • For the first time, an entire synthetic three-dimensional retina has been generated from a culture of mouse embryonic stem cells. Unexpectedly, differentiation of this synthetic retina involved self-patterning and self-formation. This result opens novel prospects for the transplantation of artificial retinal tissues at various stages of development to treat retinal degeneration [Eiraku et al 2011].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Red-green color vision defects are inherited in an X-linked manner.

Risk to Family Members

This section is written from the perspective that clinical testing for this disorder is available and results can be used for clinical purposes. However, it is the responsibility of the clinician to ascertain whether such testing is available for a specific patient.— ED.

Parents of a proband

  • The father of a color-blind male is neither color blind nor a carrier of the mutation.
  • In a family with more than one affected individual, the mother of an affected male is an obligate carrier.
  • If pedigree analysis reveals that the proband is the only affected family member, it should be assumed that the mother is a carrier because de novo mutations have not been described in red-green color vision defects.
  • Female carriers rarely have problems with color vision defects, but minor abnormalities may occasionally be found on color vision testing. Some female carriers may have defective red-green color vision as a result of skewed X-chromosome inactivation (see Penetrance).

Sibs of a proband

  • Because the mother of a proband is an obligate carrier of the mutation, the chance of transmitting the mutation in each pregnancy is 50%.
    • Male sibs who inherit the mutation will be affected; female sibs who inherit the mutation will be carriers.
  • If the proband is a homozygous female, each female sib is at a 50% risk of being a carrier and a 50% risk of having red-green color blindness.

Offspring of a proband

  • Male probands will pass the mutation to all of their daughters, who will be carriers, and to none of their sons.
  • Homozygous females will pass the mutation to all of their offspring; sons will be affected and daughters will be carriers.

Other family members of a proband. The proband's maternal aunts may be at risk of being carriers and the aunts' offspring, depending upon their gender, may be at risk of being carriers or of having color vision defects.

Carrier Detection

If the disease-causing mutation in the family has been identified, carrier testing for at-risk family members is possible through laboratories offering either testing for the gene of interest or custom testing.

Related Genetic Counseling Issues

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutation has been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Red-Green Color Vision Defects: Genes and Databases

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Red-Green Color Vision Defects (View All in OMIM)

300821OPSIN 1, MEDIUM-WAVE-SENSITIVE; OPN1MW
300822OPSIN 1, LONG-WAVE-SENSITIVE; OPN1LW
300824OPN1LW AND OPN1MW GENES, CONTROLLER OF
303800COLORBLINDNESS, PARTIAL, DEUTAN SERIES; CBD
303900COLORBLINDNESS, PARTIAL, PROTAN SERIES; CBP

Molecular Genetic Pathogenesis

High-resolution retinal imaging was employed to examine retinal cones in two males with the p. Cys203Arg mutation in the green opsin genes. Significant reduction in cone density and thinning of the outer nuclear layer compared to normal individuals were observed. This confirms previous results that this mutation causes loss of function of the opsin and association with color vision deficiency [Carroll et al 2009, Mizrahi-Meissonnier et al 2010].

Normal allelic variants. The normal red and green gene clusters observed in males with normal color vision are shown in Figure 4 (reviewed in Sharpe et al [1999], Motulsky & Deeb [2001], Neitz & Neitz [2004]). The red and green pigment genes are approximately 15 and 13 kb in length, respectively, and the intergenic region is approximately 25 kb in length. Sequence variants other than the polymorphisms at amino acid position 180 (see Genotype-Phenotype Correlations) have not been shown to be associated with common variation in normal red-green color vision [Winderickx et al 1993]. At each polymorphic site in the red pigment gene, the less common allele is derived from the green pigment gene and vice versa, indicating frequent sequence exchange between these two highly homologous genes.

OPN1MW has six exons (reference sequence NM_000513.2) and encodes the 364-amino acid green sensitive opsin protein (reference sequence NP_000504.1). OPN1LW has six exons (reference sequence NM_020061.4) and encodes the 364-amino acid red-sensitive opsin (reference sequence NP_064445.1). See review by Gardner et al [2010].

Pathologic allelic variants

  • Deletions and hybrid genes are generated by unequal crossing over between the highly homologous red and green pigment genes and are by far the most common causes of red-green color vision defects.
  • The red/green pigment gene clusters that are associated with protan color vision deficiencies are shown in Figure 5A (reviewed in Sharpe et al [1999], Motulsky & Deeb [2001], Neitz & Neitz [2004]). These clusters are characterized by replacement of the red pigment gene with a red-green hybrid gene that encodes a green-like pigment (resulting in protanomaly or protanopia). The clusters associated with deutan color vision defects (Figure 5B) are characterized by either deletion of the green pigment genes (deuteranopia) or replacement of the green pigment gene with a green-red hybrid gene that encodes a red-like pigment (deuteranomaly and deuteranopia). If the green-red hybrid gene encodes a pigment that is identical or nearly identical in wavelength of maximal absorption (λmax) to that encoded by the normal gene in the cluster, more severe dichromatic color vision deficiency may result [Neitz et al 1996]. Hybrid genes that occupy the third or more distal positions are not expressed and do not affect the red-green color vision phenotype [Hayashi et al 1999].
  • A -71A>C substitution in the green gene promoter was found to be common among Japanese subjects with deutan color vision deficiency (55 out of 447 deutans). No other mutations were found in the red or green opsin genes [Ueyama et al 2009]. In rare cases, an inactivating point mutation (e.g., c.607T>C, p.Cys203Arg, Figure 6, cluster 7) is a cause of color vision deficiency [Winderickx et al 1992b].

Table 2. Selected OPN1MW and OPN1LW Allelic Variants

Class of Variant AlleleDNA Nucleotide Change
(Alias 1)
Protein Amino Acid Change Reference Sequences 2
Normal variant in red pigment genec.538T>G
(540T>G)
p.Ser180Ala [Winderickx et al 1992b]NM_020061​.4
NP_064445​.1
Normal variants in green pigment genec.538T>G
(540T>G)
p.Ser180Ala [Winderickx et al 1992b]NM_000513​.2
NP_000504​.1
g.153,448,055A>C
(-71A>C)
In promoter [Ueyama et al 2003]NG_011606​.1
Pathologic variants in green pigment genec.607T>C
(609T>C)
p.Cys203ArgNM_000513​.2
NP_000504​.1
c.529T>Cp.Trp177Arg

Note on variant classification: Variants listed in the table have been provided by the author(s). GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1. Variant designation that does not conform to current naming conventions

2. Gardner et al [2010]

Normal gene product. The common variation at position p.Ser180Ala represents normal opsin proteins but the two alleles encode opsins with slightly different λmax (~5 nm). The -71 promoter variant (g.153,448,055A>C) encodes a normal opsin perhaps at lower level of transcription.

Abnormal gene product. The OPN1MW p.Cys203Arg and p.Trp177Arg variants encode non-functional opsins, resulting in non-functional and unstable cone photoreceptors.

See also Suggested Reading.

References

Literature Cited

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Suggested Reading

  1. Carrol J. Focus on molecules: the cone opsins. Exp Eye Res. 2008;86:865–6. [PubMed: 17981267]
  2. Cole BL. Assessment of inherited colour vision defects in clinical practice. Clin Exp Optom. 2007;90:157–75. [PubMed: 17425762]
  3. Deeb SS. The molecular basis of variation in human color vision. Clin Genet. 2005;67:369–77. [PubMed: 15811001]
  4. Deeb SS. Genetics of variation in human color vision and the retinal cone mosaic. Curr Opin Genet Dev. 2006;16:301–7. [PubMed: 16647849]
  5. Neitz J, Neitz M. The genetics of normal and defective color vision. Vision Res. 2011;51:633–51. [PMC free article: PMC3075382] [PubMed: 21167193]
  6. Swaroop A, Kim D, Forrest D. Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci. 2010;11:563–76. [PubMed: 20648062]

Chapter Notes

Acknowledgments

The preparation of this review was supported by National Institutes of Health grant number EY08395.

Revision History

  • 29 September 2011 (me) Comprehensive update posted live
  • 19 September 2005 (me) Review posted to live Web site
  • 19 July 2004 (sd) Original submission
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