Achromatopsia, or total color blindness, is a rare visual disorder characterized by the absence or impairment of color vision. There are two main types of achromatopsia: complete achromatopsia (type 2) and incomplete. Achromatopsia (ACHM) is a rare vision disease that affects approximately one in 30.000 people.
Achromatopsia genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Complete Achromatopsia (Type 2)
Individuals with complete achromatopsia have a complete absence of color vision, seeing the world in shades of gray. This condition is typically caused by mutations in several genes, including CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H, which are involved in the function of cone cells in the retina. Cone cells are responsible for color vision in bright light conditions.
Additional features of complete achromatopsia may include reduced visual acuity, increased sensitivity to light (photophobia), and nystagmus (involuntary eye movement). Individuals with complete achromatopsia often rely on their rod cells for vision in low-light conditions.
Management involves addressing visual symptoms, such as providing tinted lenses to reduce light sensitivity. There is currently no cure for achromatopsia, but adaptive strategies and visual aids can help individuals manage their condition.
Incomplete Achromatopsia
Incomplete achromatopsia, also known as partial achromatopsia or atypical achromatopsia, is a milder condition where some color discrimination is present but still significantly impaired. Individuals with incomplete achromatopsia may have difficulty distinguishing certain colors or may only perceive a limited range of colors.
The severity of symptoms can vary, and individuals may experience photophobia, reduced visual acuity, and nystagmus. The genetic basis of incomplete achromatopsia can also involve mutations in the same genes associated with complete achromatopsia.
Management and support for individuals with incomplete achromatopsia are similar to those with complete achromatopsia, including using tinted lenses, adaptive strategies, and visual aids.
Both types of achromatopsia are genetic disorders, and genetic testing can be conducted to identify the specific genetic mutations involved. Genetic counseling is recommended for individuals and families affected by achromatopsia to understand the inheritance pattern and make informed decisions.
While no cure exists for achromatopsia, ongoing research explores potential therapeutic approaches, including gene therapies, to correct the genetic mutations underlying the condition.
Up to 6 genes related to ACHM have been described (CNGA3, CNGB3, ATF6, GNAT2, PDE6C, and PDE6H). All of them, except ATF6, encode proteins involved in signal phototransduction, transforming light signals into nerve impulses.
Most cases (about 90%) of achromatopsia are due to pathogenic variants in CNGA3 and CNGB3, both of which encode for the alpha and beta subunits of heterotetrameric channels, known as CNG channels, involved in the phototransduction cascade of photoreceptors, specifically cones.
The ATF6 protein localizes to the endoplasmic reticulum and is involved in endoplasmic reticulum stress and the response to unfolded proteins.
The PDE6C and PDE6H genes encode for the alpha and gamma subunits of cyclic GMP phosphodiesterase (the energy molecule required by CNG channels). The CNG channels of the photoreceptor cells open or close and regulate the transduction of the light signal, causing the CNG channels to open or close.
Currently, there are about 100 pathogenic variants in CNGA3 and another 100 in CNGB3 in the scientific literature. The number of pathogenic variants identified for the ATF6, PDE6C, and PDE6H genes is less than 100. All the variants follow an autosomal recessive inheritance pattern, and cases of compound heterozygotes manifesting ACHM have been observed.
The Genetic Test for Achromatopsia of Diagnostiki Athinon analyzes the six most frequent pathogenic mutations of the ATF6 gene plus the 13 most frequent pathogenic mutations of the CNGA3 gene plus the five most frequent pathogenic mutations of the CNGB3 gene plus the one most frequent pathogenic mutation of PDE6C gene plus the one most frequent pathogenic mutation of PDE6H gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
