Genetic Basis of LCA

Genetic Basis of LCA

IRDs are caused by a gene mutation that is inherited from a parent. This led to the title of “Inherited Retinal Disease”. In the case of IRDs, the mutation affects genes that play an essential role in normal retinal development and functioning, leading to the degeneration of photoreceptors and other retinal cells and associated vision loss.

LCA is the result of a mutation in one of at least 17 different genes, which is why it is called a “genetic” or “inherited” disorder. Both rod and cone cells can be affected by the mutations and therefore can degenerate and die. In all cases, the retina’s ability to develop and function properly is impaired, resulting in visual impairment. LCA is a very rare condition which is estimated to affect around 1 in 80,000 in the population. Forms of LCA are caused by a mutation in one of up to 18 genes that are important for retinal function. Both rod and cone cells can be affected by the mutations and therefore can degenerate and die.

Regardless of the mutation involved, visual impairment is due to impairments in the retina’s ability to develop and function properly. It is usually inherited in an autosomal recessive manner. However, there are rare incidences where the inheritance pattern may be autosomal dominant. You can learn more about inheritance patterns here: Inheritance Patterns.

Some genes that are implicated in LCA can also be connected to other IRDs. For example, different mutations in the GUCY2D gene can result in either cone-rod dystrophy or in LCA. You can see the list of genes currently known to be associated with LCA here.

Genetic testing is of utmost importance for many IRDs due to their genetic origin. Genetic testing can aid in diagnosis and, critically, it can determine if individuals have a specific mutation that may mean they are eligible for a clinical trial or even treatable by specific gene therapies.

Watch this short video from the National Eye Institute/National Institutes of Health (NEI/NIH) about vision in families: