Color blindness, also known as color vision deficiency, is the decreased ability to see color or differences between colors. It is most often caused by abnormalities in the genes responsible for the production of cone photoreceptor cells in the retina. There are several types of color blindness depending on which color cones are impacted.
Causes of Color Blindness
In the human eye, there are two types of photoreceptor cells – rods and cones. Rods are responsible for vision in low light. Cones are responsible for color vision and function best in bright light. There are three types of cones that each contain a different photopigment, which is sensitive to different wavelengths of light:
- S cones – sensitive to short wavelengths (blue)
- M cones – sensitive to medium wavelengths (green)
- L cones – sensitive to long wavelengths (red)
Normal color vision requires all three types of cone cells to function properly. Color blindness occurs when there is an abnormality in one or more of the cone photopigments. The most common causes are:
- Mutation in the genes responsible for the photopigments in cone cells
- Absence of one or more types of cone cells
- Damage or deterioration of cone cells
Genetic mutations that impact cone cells are the most common cause of inherited color blindness. The genes involved are located on the X chromosome. As a result, color blindness is much more prevalent in men.
Types of Color Blindness
There are three main types of inherited color blindness based on which photopigments are impacted:
- Red-green color blindness – caused by abnormal L or M cone cells. This is the most common type and there are several subtypes based on the genetic cause and severity of L or M cone impairment. Subtypes include:
- Protanomaly (abnormal L cones)
- Protanopia (missing L cones)
- Deuteranomaly (abnormal M cones)
- Deuteranopia (missing M cones)
- Blue-yellow color blindness – caused by abnormal S cone cells. This is a very rare type. Subtypes include:
- Tritanomaly (abnormal S cones)
- Tritanopia (missing S cones)
- Complete color blindness – caused by abnormalities in two or more photopigments (very rare)
Color Blindness Gene Sequences
There are several genes involved in the production of cone photopigments that when mutated can cause color blindness. The main genes and their chromosomal locations are:
| Gene | Photopigment | Chromosomal Location |
|---|---|---|
| OPN1LW | L cone (Red) | Xq28 |
| OPN1MW | M cone (Green) | Xq28 |
| OPN1SW | S cone (Blue) | 7q32.1 |
The OPN1LW and OPN1MW genes encoding the L and M cone pigments are located next to each other on the X chromosome. There are several common gene rearrangements that can occur between these two genes that cause red-green color blindness, which accounts for over 99% of cases.
OPN1LW gene
The OPN1LW gene spans over 18,000 base pairs on chromosome Xq28 and contains six exons that code for the L cone opsin pigment. Mutations in this gene typically result in abnormalities in the L cones and cause protan color blindness (protanopia or protanomaly). There are over 100 identified mutations in OPN1LW associated with impaired L cone function and reduced red color vision.
Some of the most common OPN1LW mutations include:
- C203R missense mutation in exon 3
- P307L missense mutation in exon 5
- C522F missense mutation in exon 5
- A180P missense mutation in exon 3
Additionally, there are several large deletions and rearrangements that inactivate the OPN1LW gene entirely leading to protanopia. This includes deletions of the exon 1-3 region of OPN1LW or fusion of OPN1LW with the first one or two exons of OPN1MW.
OPN1MW gene
The OPN1MW gene is located adjacent to OPN1LW on chromosome Xq28 and also contains six exons encoding the M cone opsin. Mutations in OPN1MW lead to defective M cones and cause deutan color blindness (deuteranopia or deuteranomaly). Over 60 mutations have been found that impair M cone function and reduce green color vision. Some examples include:
- C203R missense mutation in exon 3
- P307L missense mutation in exon 5
- Y236X nonsense mutation in exon 4
- R330Q missense mutation in exon 5
In addition, deletion or fusion of the first exon or first two exons of OPN1MW with OPN1LW accounts for many cases of deuteranopia.
OPN1SW gene
The OPN1SW gene encoding the blue S cone opsin is located on chromosome 7q32.1. It also contains six exons spanning around 10,000 base pairs. Mutations in this gene lead to defective S cones and tritan color blindness, although this is very rare. Reported mutations include:
- N94K missense mutation in exon 2
- R233W missense mutation in exon 4
- A241S missense mutation in exon 4
- L56P missense mutation in exon 2
Genetic Testing
Genetic testing is available to diagnose and determine the exact type of color blindness. This can involve:
- Gene sequencing – sequencing the exons of the OPN1LW, OPN1MW, and OPN1SW genes to look for known pathogenic variants.
- Deletion/duplication analysis – testing for large deletions, insertions, or rearrangements between OPN1LW and OPN1MW.
- Genetic panels – kits that combine sequencing and deletion/duplication analysis of all three genes.
Genetic testing provides a definitive diagnosis and allows for genetic counseling regarding likelihood of passing on color blindness mutations. It can also guide treatment, as some types of color blindness may be treatable with special tinted filters.
Treatment and Management
While there is no cure for inherited color blindness, there are ways to manage it with accommodations and aids. Some options include:
- Special tinted filters and contact lenses to increase contrast between colors
- Apps and tools to identify colors
- Occupational aids like high visibility markers or lighting adjustments
- Counseling and support groups
- Gene therapy research for therapies that can restore cone function
People with color blindness can live normal lives with just a few adjustments based on their individual needs and type of color vision deficiency. Staying up to date on the latest genetic research for treatment is also important.
Conclusion
In summary, color blindness is most commonly caused by genetic mutations in the OPN1LW, OPN1MW, and OPN1SW genes that lead to malfunction of cone cells in the retina. Sequencing and analysis of these three genes located on the X and chromosome 7 can diagnose the specific type of color blindness and guide management options. While there is currently no cure, many people with color blindness adapt well and lead perfectly normal lives with just a few accommodations. Gene therapy may offer a potential treatment approach in the future.