BEST1

BEST1 provides the blueprint for bestrophin-1, a channel protein located mainly in the retinal pigment epithelium (RPE), the layer of cells that nourishes the retina's photoreceptors. Bestrophin-1 helps move charged particles such as chloride and bicarbonate across these cells and supports the eye's normal light-processing cycle. The gene is known by several other names in medical records, including VMD2, ARB, and RP50. When bestrophin-1 does not work correctly, the connection between the RPE and the photoreceptors it supports is disrupted, which is where the disease process begins.

Most people with a BEST1 change notice changes in central vision, the sharp vision used for reading and recognizing faces, rather than the loss of side vision seen in classic retinitis pigmentosa. A common early sign is a yellowish, egg-yolk-like deposit in the macula, the central part of the retina, which can later break up or thin over time. BEST1 changes are linked to several distinct presentations, including juvenile-onset Best disease, adult-onset vitelliform macular dystrophy, and autosomal recessive (definition: An inheritance pattern where a person needs an altered copy of a gene from both parents to be affected. Parents with only one copy are usually unaffected carriers.) bestrophinopathy (ARB). A rarer, dominant presentation called autosomal dominant (definition: An inheritance pattern where a single altered copy of a gene, from just one parent, is enough to cause the condition.) vitreoretinochoroidopathy (ADVIRC) has been associated with a different, gain-of-function effect and with a higher chance of nearsightedness and thinning of the photoreceptor (definition: A light-sensing cell in the retina. Rods (used for night and peripheral vision) and cones (used for color and detail) are the two types.) layer. Uncommonly, BEST1 has also been reported in connection with retinitis pigmentosa, reflected in its alias RP50. The age at which symptoms begin and how quickly they progress vary widely from person to person.

BEST1 is a well-recognized and relatively common cause of inherited macular dystrophy across many populations, appearing among the leading genes in several large clinic and cohort studies. Researchers have shown that dominant and recessive BEST1 conditions form a continuous spectrum rather than fully separate diseases, with recessively inherited vitelliform dystrophy falling between dominant Best disease and ARB. In one European registry study, most BEST1 diagnoses followed a dominant inheritance pattern, while a smaller share were recessive. Animal studies in dogs and in a nonhuman primate carrying a BEST1 variant reproduce the human macular changes closely, which helps scientists study how the disease develops.

Predicting an individual's outcome from their specific BEST1 variant remains difficult, and attempts to separate recessive and dominant disease by variant type alone have not produced clear rules. The underlying effects of different variants range from loss of the protein's function to gain of a new, harmful activity, and this influences which therapeutic strategy might eventually suit a given person. In rare cases, a person may carry variants in BEST1 alongside a second retinal gene, which can blur the clinical picture and complicate diagnosis and counseling.

No therapy that targets BEST1 has yet been approved, and current care focuses on monitoring and supporting remaining vision. In dogs with naturally occurring BEST1 disease, gene therapy (definition: A treatment that delivers a working copy of a gene into cells to take over for a copy that isn't functioning properly.) delivered to the RPE corrected the early microscopic changes and reversed larger lesions when given at a certain stage, making this a promising translational model. In laboratory work using cells grown from a patient, researchers have begun testing precise gene-editing (base editing) to correct a dominant BEST1 variant, though efficiency remains modest and this is early-stage research, not a treatment. Stem cell-derived RPE models are also being used to study how different BEST1 variants behave and which correction strategies might fit each mutation class. A broad review of advanced therapies for inherited retinal disease found some encouraging signals from gene, cell, and stem cell approaches overall, but concluded the evidence is not yet strong enough for general recommendations.

• Gene therapy in a canine model of Best disease

  Preclinical animal research.

  What was found:

  The disease was shown to affect the RPE-photoreceptor interface, and gene therapy corrected early changes and reversed larger lesions when given at a specific stage.

  Why it matters:

  It provides a strong translational model supporting development of gene-based treatments for Best disease.

  Limitation: Results are in dogs, not humans, and do not establish safety or benefit in people.

• Editing a dominant BEST1 variant in patient-derived cells

  Laboratory (cell-based) research, preprint.

  What was found:

  Correcting the variant normalized cell behavior, and a delivered base editor edited the mutant copy with a maximum efficiency of about 13 percent.

  Why it matters:

  It shows early progress toward correcting dominant BEST1 disease, which is harder to treat with simple gene replacement.

  Limitation: Editing efficiency was modest, the work is in cultured cells only, and the preprint is not peer-reviewed.

• A spectrum linking dominant Best disease and recessive bestrophinopathy

  Small case series combined with a literature meta-analysis.

  What was found:

  Recessively inherited vitelliform dystrophy fell clinically between dominant Best disease and autosomal recessive bestrophinopathy, and variant type alone did not reliably separate the groups.

  Why it matters:

  It supports viewing BEST1 conditions as one continuous disease spectrum, which helps explain why the same gene can produce different diagnoses.

  Limitation: Only a small number of new patients were examined, limiting how firmly conclusions can be drawn.

• Dominant and recessive inheritance in a retinal disease registry

  Cross-sectional observational registry study.

  What was found:

  BEST1 was mostly associated with dominant inheritance and chiefly caused Best disease, though a minority of cases were recessive.

  Why it matters:

  It shows why inheritance and counseling for BEST1 families depend on the specific variant rather than a single fixed pattern.

  Limitation: Findings come from one region and center and may not represent all populations.

• Estimating how common BEST1 retinopathy is worldwide

  Review and meta-analysis (preprint, not yet peer-reviewed).

  What was found:

  BEST1 disease was found across the world, with prevalence and the share of recessive (biallelic) cases differing by geography.

  Why it matters:

  It underscores that BEST1 is among the larger inherited retinal disease populations, informing the scale of unmet need for therapies.

  Limitation: Estimates rely on modeling and existing reports, and this preprint has not completed peer review.

Because BEST1 disease can be passed on in either a dominant or a recessive pattern, the implications for children, siblings, and other relatives differ depending on the variant, and a genetic counselor can explain the specific risk in your family. Some forms, such as juvenile-onset Best disease, can begin in childhood, so families may wish to discuss timing of eye examinations for younger relatives with a specialist.

• Does my specific BEST1 variant appear to act through a dominant or a recessive pattern, and what does that mean for my relatives?
• Which type of bestrophinopathy best matches my clinical and imaging findings?
• How often should I have retinal imaging to monitor changes in my central vision?
• Are there signs or symptoms I should report between visits?
• Is my genetic result fully explained by BEST1, or could a second gene be contributing?
• Would participating in a natural history study or registry be worthwhile in my situation?

Confirming the specific BEST1 variant through genetic testing, and reviewing what it means with a genetic counselor, can clarify inheritance and what to watch for. Regular monitoring with a retinal specialist, including retinal imaging, helps track macular changes over time. To explore whether any current studies may be relevant, you can use RP Hope's Clinical Trials Finder with BEST1 preselected, where eligibility can be reviewed with the study team.