Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants

Inclusion Criteria: Participants must meet all the following inclusion criteria at the Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

1. Willing to participate in the study and able to communicate consent during theconsent process

2. Willing and able to complete all applicable Registry/Screening Visit assessments

3. Age ≥ 4 years

4. Must have a single gene on the RD Rare Gene List which meets one of the GeneticScreening Criteria below based on a genetic report* from a clinically certified lab (or from a research lab which has been approved by the study Genetics Committee):

Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are homozygous or heterozygous in trans

OR

Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and meets all the following additional informatic criteria that is consistent with likely segregation in trans:

1. Investigator confirms genotype and phenotype are consistent with autosomal recessiveinheritance

2. The 2 disease-causing variants have not been reported in cis in variant databases

3. No additional potentially pathogenic variants were found on the gene (and thesequencing data for the gene were sufficiently robust to detect any additionalpotentially pathogenic variants)

4. No potentially pathogenic variants were found in other common, likely candidategenes for the proposed condition

OR

Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1 disease-causing variant

Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into the genetic screening phase:

1. Both eyes must have a clinical diagnosis of retinal dystrophy

2. Both eyes must permit good quality photographic imaging (e.g., but not limited to,clear ocular media, adequate pupil dilation, stable fixation)

Exclusion Criteria:

Participants must not meet any of the following exclusion criteria at the Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

1. History of more than 1 year of cumulative treatment, at any time, with an agentassociated with pigmentary retinopathy including amiodarone, chloroquine,deferoxamine, hydroxychloroquine, pentosan polysulfate, tamoxifen, and deferoxamineNote: Since this is an observational study, pregnant women will not be specificallyexcluded from participation. However, minors that are pregnant shall be precludedfrom participation until they become the age of majority.

Ocular Exclusion Criteria:

If either eye has any of the following ocular exclusion criteria at the Registry/Screening Visit, then the participant is not eligible to enroll into the genetic screening phase:

1. Current vitreous hemorrhage

2. Current complications of pathological myopia (for example, but not limited to,myopic maculopathy including atrophy, scar, choroidal neovascularization, schisis)that could inhibit ability to obtain good quality photographic imaging

3. History of intraocular surgery (for example, but not limited to, cataract surgery,vitrectomy, penetrating keratoplasty, or LASIK) within 3 months ofRegistry/Screening Visit

4. Current or any history of confirmed diagnosis of glaucoma (for example, but notlimited to, glaucomatous VF changes or nerve changes, or history of glaucomafiltering surgery)

5. Current or any history of retinal vascular occlusion or proliferative diabeticretinopathy

6. History or current evidence of ocular disease that, in the opinion of theInvestigator, may confound assessment of visual function (for example, but notlimited to, tractional or rhegmatogenous retinal detachment, any vitreoretinalsurgery, retinal vascular occlusion, proliferative diabetic retinopathy)

7. The following medications and treatments are prohibited as they can affectprogression of retinitis pigmentosa (RP). The participant must not have received thefollowing treatments: Any use of ocular stem cell or gene therapy Any treatment with ocriplasmin Treatmentwith Ozurdex (dexamethasone), Iluvien, or Yutiq (fluocinolone acetonide)intravitreal implant

8. The following medications and treatments are excluded within the specifiedtimeframe:

Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Registry/Screening Visit date)

Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Registry/Screening Visit date is at least 5 times the half-life of the given product)