PRPH2-Associated Disease

About the Disease

Mutations in PRPH2 are a relatively common cause of several inherited retinal degenerations, including: retinitis pigmentosa (RP), pattern macular dystrophies (PMDs), cone-rod dystrophies (CRDs), and central areolar choroidal dystrophy (CACD).

PRPH2 is a protein encoded by the PRPH2 gene. PRPH2, sometimes referred to as peripherin/rds, peripherin-2, or RDS, is essential for the function and survival of rod and cone photoreceptors. PRPH2 sits in the membrane, or shell, of rod discs and cone lamellae, which are layered structures that make up the outer segments. Rod discs and cone lamellae contain large amounts of light-sensing proteins, like rhodopsin and cone opsins, and are the site of light capture. PRPH2 helps to provide support and a curved shape to these critical visual structures. Researchers have found that mice that lack both copies of PRPH2 do not form rod outer segments and form defective cone outer segments. Mice missing one copy of PRPH2 have defective rod and cone outer segments. In both cases mice experience death of photoreceptor cells and a decrease in visual function.

Symptoms

In most cases, PRPH2-associated disease is late-onset. Affected individuals often notice changes to their vision in their 30s-50s. The exact onset, symptoms, and prognosis are often different for each person and depend on the disease that they have been diagnosed with. One of the hallmarks of PRPH2-associated disease is its heterogeneity and variability. Individuals with the exact same genetic mutation—even siblings or other related individuals—may have very different symptoms and even different diagnoses. Researchers still do not understand why mutations in PRPH2 can cause so many different diseases and variability in symptoms. 

Below is an example of how one's vision may be impacted by a PRP2-associated disease.

How the Disease is Inherited

PRPH2-associated disease is usually inherited in an autosomal dominant manner. This means that having a single damaging PRPH2 mutation is sufficient to cause symptoms and disease. Autosomal dominant diseases are passed down from an affected parent who has the mutated gene. Each of their children has a one in two chance of inheriting the condition.

When a person inherits two damaging PRPH2 mutations, which happens rarely, they may be diagnosed with Leber congenital amaurosis (LCA) or early onset severe retinal dystrophy (EOSRD). Individuals who carry two PRPH2 mutations develop disease significantly earlier and have more severe symptoms.

PRPH2-associated disease may also be misdiagnosed as Stargardt disease (SD) or dry age-related macular degeneration (AMD).

To date, more than 200 damaging mutations in PRPH2 have been identified and linked to retinal disease.

Living with the Disease

There are many services and accommodative and assistive resources available to people and families with a PRPH2-associated disease. Visit the Foundation’s Low Vision Resources page to learn about many of these resources. A low vision specialist can help recommend the resources that are right for you.

More information on living with PRPH2-associated disease is in the Newly Diagnosed section of this Web site.

Research & Clinical Trials

There are currently no clinical trials that are specifically focused on PRPH2-associated disease, though there are some gene agnostic therapies in or nearing clinical trials that might be relevant to people with PRPH2-associated retinal disease.

To learn more about current research and new potential therapies early in development, please consider attending our upcoming PRPH2 and Associated Retinal Diseases Workshop on March 29–31, 2023, at the Hilton La Jolla Torrey Pines in San Diego, CA. Registration information can be found at www.FightingBlindness.org/PRPH2Workshop.

Treatments

There are currently no treatments for PRPH2-associated disease.