Inherited ocular disease includes a broad spectrum of conditions affecting the retina, retinal pigment epithelium (RPE), optic nerve, lens, cornea, and ocular development. These disorders may present as isolated ophthalmic phenotypes (e.g., retinitis pigmentosa, cone-rod dystrophy, congenital cataracts, corneal dystrophies, inherited glaucoma) or as syndromic conditions with systemic involvement (e.g., ciliopathies, peroxisomal disorders, mitochondrial disease, renal/neurologic syndromes).
The PreCheck Health Services Comprehensive Ocular Disease Panel (331 genes) is a germline, targeted exome assay intended for constitutional DNA (e.g., peripheral blood or saliva). The panel prioritizes genes with established relevance to inherited retinal degeneration, macular dystrophies, optic neuropathies, anterior segment dysgenesis, lens and corneal disorders, and multisystem syndromes where ocular findings are a primary feature.
❖ Inherited Retinal Degeneration (IRD): rod-cone dystrophy/retinitis pigmentosa, cone/cone-rod dystrophy, LCA/early-onset severe retinal dystrophy, stationary night blindness, chorioretinal dystrophies, macular dystrophies.
❖ Macular and RPE Disorders: Stargardt/ABCA4-spectrum disease, BEST1-related retinopathies, EFEMP1/TIMP3-associated macular disease patterns.
❖ Progressive Optic Nerve Disorders: hereditary optic atrophy and optic neuropathy phenotypes (including syndromic presentations).
❖ Anterior Segment and Developmental Eye Disorders: aniridia-like phenotypes, microphthalmia/anophthalmia spectrum, coloboma, Axenfeld-Rieger spectrum, congenital glaucoma risk.
❖ Corneal Disorders: corneal dystrophy/thinning phenotypes and cornea-associated syndromes.
❖ Lens Disorders: congenital/juvenile cataracts and syndromic cataract presentations.
❖ Suspected Syndromic Ocular Disease: ocular findings with renal, neurologic, skeletal, metabolic, or developmental features (e.g., ciliopathies, peroxisomal disorders, mitochondrial disease).
1. Phototransduction & Retinal Signal Transduction (rod/cone function)
❖ RHO, GNAT1, GNAT2, PDE6A, PDE6B, PDE6C, PDE6G, PDE6H, CNGA1, CNGA3, CNGB1, CNGB3, GRK1, SAG, RGS9, RGS9BP, TRPM1, GRM6, GPR179
2. Visual Cycle, RPE Biology, and Retinoid Metabolism
❖ RPE65, LRAT, RLBP1, RDH5, RDH11, RDH12, RBP4, STRA6
3. Ciliary Structure/Intraflagellar Transport and Syndromic IRD (ciliopathies)
❖ CEP290, CC2D2A, IQCB1, LCA5, NPHP1/3/4, SDCCAG8, TTC8, TMEM67, TMEM231, WDPCP, WDR19, IFT140, IFT172, IFT27, TCTN1/2/3, BBS1/2/4/5/7/9/10/12, MKKS, MKS1, LZTFL1, VPS13B
4. Retinal Structure, Disc Morphogenesis, and Degeneration Pathways
❖ PRPH2, RP1, RP1L1, EYS, CRB1, PROM1, PRCD, IMPG1, IMPG2, FAM161A, SPATA7, RD3
5. Lens/Cataract and Crystallin/Structural Proteins.
❖ CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS, MIP, LIM2, BFSP1, BFSP2, HSF4, FYCO1, EPHA2, GALK1
6. Cornea, Extracellular Matrix, and Corneal Dystrophy Genes
❖ TGFBI, KRT3, KRT12, KERA, CHST6, ZEB1, ZNF469, PRDM5, TACSTD2
7. Optic Atrophy / Mitochondrial and Neuro-ophthalmic Syndromes
❖ OPA1, OPA3, ACO2, POLG, TWNK, SSBP1, DNAJC30, RRM2B, AFG3L2, SLC25A46
8. Metabolic/Peroxisomal and Multisystem Syndromes with Ocular Findings
❖ PEX1/2/3/5/6/7/10/12/13/14/16/19/26, PHYH, PNPLA6, HGSNAT, CLN3, PPT1, TPP1, MFSD8
Parameter Description
Genes Analyzed 331 Ocular disease-related genes.
Technology Platform Illumina NGS (Hybrid-Capture Target Enrichment).
Coverage Metrics >98% bases at ≥20× read depth.
Variant Types Detected SNVs and small indels (≤20 bp) within coding exons ±10 bp intronic boundaries.
Reference Genome GRCh38/hg38.
Bioinformatics Pipeline SeqOne™, ACMG/AMP compliant.
Confirmatory Testing Sanger sequencing or orthogonal method as indicated.
Turnaround Time ~10 calendar days.
Quality Metrics Read quality ≥Q30; allelic balance ≥0.3; minimum coverage 20×.
1. Diagnostic Clarity and Prognosis
❖ Resolves “idiopathic” ocular disease by identifying a molecular etiology.
❖ Distinguishes overlapping phenotypes (e.g., rod-cone dystrophy vs cone-rod dystrophy vs stationary night blindness), enabling more accurate prognosis and surveillance.
2. Management, Surveillance, and Care Planning
❖ Supports gene-informed monitoring (retina vs optic nerve vs anterior segment involvement).
❖ Enables earlier systemic evaluation when syndromic genes are implicated (renal, neurologic, metabolic risk depending on gene findings).
3. Family Risk Assessment and Reproductive Planning
❖ Defines inheritance (AR/AD/X-linked/mitochondrial), guiding recurrence risk counseling and cascade testing.
Comprehensive ocular disease genetic testing provides clinically actionable information across ophthalmology (retina, cornea, glaucoma, neuro-ophthalmology, pediatrics), optometry, medical genetics, genetic counseling, and primary care. Results directly influence diagnostic clarification, management planning, surveillance strategies, therapeutic eligibility, and family counseling.
Risk Stratification and Diagnostic Clarification
Identify pathogenic or likely pathogenic variants underlying inherited retinal degeneration, macular dystrophy, optic neuropathy, anterior segment dysgenesis, congenital cataract, and corneal dystrophy—distinguishing hereditary causes from acquired or environmental contributors (e.g., inflammatory, infectious, traumatic, toxic, or age-related processes). Refine differential diagnoses generated by exam findings, OCT, ERG, fundus autofluorescence, and ocular imaging, enabling the transition from a “suspected” ocular condition to a definitive gene-based diagnosis that may indicate syndromic disease requiring broader surveillance (e.g., ciliopathies such as BBS genes/CEP290/NPHP genes, peroxisomal disorders such as PEX genes, lysosomal/neuronal ceroid lipofuscinosis genes such as CLN3/PPT1/TPP1, or renal/neurologic involvement in NPHP/SDCCAG8-associated disease).
Family Risk Assessment, Cascade Testing, and Reproductive Counseling
Clarify recurrence risk for families and identify at-risk relatives once a pathogenic variant is identified—particularly for autosomal recessive IRD (e.g., ABCA4, RPE65, CEP290, CNGB1), autosomal dominant retinal/optic/corneal disorders (e.g., PRPH2, RHO, OPA1, TGFBI, ZEB1), and X-linked disease (e.g., RPGR, CHM, NYX, RS1). Support targeted partner testing and carrier evaluation when appropriate to assess couple-level reproductive risk. Provide anticipatory guidance for gene-positive relatives who may be at risk for progressive disease, enabling earlier surveillance (e.g., baseline retinal imaging/ERG where indicated, optic nerve monitoring, or glaucoma risk assessment in relevant gene contexts).
Pharmacogenetics Testing (for drug metabolism and gene-drug interactions)
Match treatments to the patient’s metabolic phenotype (e.g., CYP2D6, CYP2C19, CYP3A5, CYP2C9), reducing the risk of adverse drug reactions and improving efficacy.
Together, these tools enable precision medicine teams to offer a fully customized, data-driven treatment plan for each patient.
Germline testing for inherited ocular disease has become an essential tool in precision medicine, enabling clinicians to identify the molecular causes of inherited retinal degeneration, macular dystrophy, optic neuropathy, anterior segment dysgenesis, congenital cataract, and corneal dystrophy syndromes. When combined with comprehensive ophthalmic examination and ocular imaging (e.g., OCT, fundus autofluorescence, ERG where appropriate), a targeted gene panel provides diagnostic clarity that surpasses clinical assessment alone—particularly in phenotypically overlapping disorders.
With high analytic performance and curated gene–disease evidence, PreCheck Health Services delivers genomic insights that refine diagnosis, guide surveillance and management strategies, and support decisions around specialty referral, systemic evaluation when syndromic disease is suspected, and reproductive risk management. Molecular findings also enable targeted cascade testing and appropriate partner evaluation when relevant.
This integrated approach enhances long-term ocular and general health care by enabling earlier, more accurate, and individualized management, ultimately improving outcomes and supporting informed planning for patients and families.
The Comprehensive Ocular Disease Panel is designed to detect single-nucleotide variants (SNVs) and small insertions and deletions in 331 genes associated with inherited ocular disease. Targeted regions for this panel include the coding exons and 10 bp intronic sequences immediately to the exon-intron boundary of each coding exon in each of these genes. Extracted patient DNA is prepared using targeted hybrid capture, assignment of a unique index, and sequencing via Illumina sequencing by synthesis (SBS) technology. Data is aligned using the human genome build GRCh38. Variant interpretation is performed according to current American College of Medical Genetics and Genomics (ACMG) professional guidelines for the interpretation of germline sequence variants using SeqOne Pipeline.
ABCA4, ABHD12, ACO2, ADAM9, ADAMTS18, ADGRV1, AFG3L2, AIPL1, ALDH1A3, ALMS1, ARL13B, ARL2BP, ARL3, ARL6, ATF6, ATOH7, ATXN7, B3GLCT, B9D1, B9D2, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BCOR, BEST1, BFSP1, BFSP2, BMP4, C1QTNF5, C2orf71, C8orf37, CABP4, CACNA1F, CACNA2D4, CAPN5, CC2D2A, CDH23, CDH3, CDHR1, CEP164, CEP290, CERKL, CHM, CHMP4B, CHN1, CHRDL1, CHST6, CISD2, CLDN19, CLN3, CLRN1, CNGA1, CNGA3, CNGB1, CNGB3, CNNM4, COL11A1, COL18A1, COL2A1, COL4A1, COL8A2, COL9A1, COL9A2, CRB1, CRX, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS, CTDP1, CTNNA1, CYP1B1, CYP4V2, DHDDS, DHX38, DNAJC30, EFEMP1, ELOVL4, ELP4, EPHA2, EYS, FAM161A, FLVCR1, FOXC1, FOXE3, FOXL2, FRAS1, FREM1, FREM2, FRMD7, FTL, FYCO1, FZD4, GALK1, GCNT2, GDF6, GJA1, GJA3, GJA8, GNAT1, GNAT2, GPR143, GPR179, GRK1, GRM6, GSN, GUCA1A, GUCA1B, GUCY2D, HCCS, HESX1, HGSNAT, HMX1, HSF4, IARS2, IFT140, IFT172, IFT27, IMPDH1, IMPG1, IMPG2, INPP5E, IQCB1, ISPD, JAM3, KCNJ13, KCNV2, KERA, KIAA1549, KIF11, KIF21A, KIZ, KRT12, KRT3, LAMB2, LCA5, LCAT, LIM2, LRAT, LRIT3, LRMDA, LRP5, LTBP2, LZTFL1, MAF, MAK, MERTK, MFRP, MFSD8, MIP, MIR184, MITF, MKKS, MKS1, MYO7A, MYOC, NDP, NHS, NMNAT1, NPHP1, NPHP3, NPHP4, NR2E3, NR2F1, NRL, NYX, OAT, OCRL, OFD1, OPA1, OPA3, OPTN, OTX2, PAX2, PAX6, PCDH15, PCYT1A, PDE6A, PDE6B, PDE6C, PDE6G, PDE6H, PEX1, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PHOX2A, PHYH, PIKFYVE, PITPNM3, PITX2, PITX3, PLK4, PNPLA6, POC1B, POLG, POMGNT1, POMT1, PORCN, PPT1, PRCD, PRDM5, PROM1, PRPF3, PRPF31, PRPF4, PRPF6, PRPF8, PRPH2, PRSS56, PXDN, RAB18, RAB28, RAB3GAP1, RAB3GAP2, RARB, RAX, RAX2, RB1, RBP4, RCBTB1, RD3, RDH11, RDH12, RDH5, RERE, RGS9, RGS9BP, RHO, RLBP1, ROBO3, RP1, RP1L1, RP2, RPE65, RPGR, RPGRIP1, RRM2B, RS1, SAG, SALL4, SCAPER, SDCCAG8, SH3PXD2B, SHH, SIL1, SIX3, SIX6, SLC16A12, SLC24A1, SLC25A46, SLC33A1, SLC38A8, SLC4A11, SLC7A14, SMOC1, SNRNP200, SOX2, SPATA7, SRD5A3, SSBP1, STRA6, TACSTD2, TBC1D20, TCTN1, TCTN2, TCTN3, TDRD7, TEAD1, TEK, TENM3, TFAP2A, TGFBI, TIMP3, TMEM126A, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67, TOPORS, TPP1, TRPM1, TRPM3, TSPAN12, TTC8, TTLL5, TTPA, TUB, TUBB3, TUBGCP4, TUBGCP6, TULP1, TWNK, UBIAD1, UNC45B, USH1C, USH1G, USH2A, VCAN, VPS13B, VSX2, WDPCP, WDR19, WFS1, WHRN, ZEB1, ZNF408, ZNF469
This test aims to detect all clinically relevant variants within the coding regions of the genes evaluated. Pathogenic and likely pathogenic variants detected in these genes should be confirmed by orthogonal methods. Detected genetic variants classified as benign, likely benign, or of uncertain significance are not included in this report. Homopolymer regions and regions outside of the coding regions cannot be captured by the standard NGS target enrichment protocols. Currently, the assay does not detect large deletions and duplications. This analysis also cannot detect pathogenic variants within regions that were not analyzed (e.g., introns, promoter and enhancer regions, long repeat regions, and mitochondrial sequence). This assay is not designed to detect mosaicism and is not designed to detect complex gene rearrangements or genomic aneuploidy events. It is important to understand that there may be variants in these genes undetectable using current technology. Additionally, there may be genes associated with ocular disease whose clinical association has not yet been definitively established. The test may therefore not detect all variants associated with ocular disease. The interpretation of variants is based on our current understanding of the genes in this panel and is based on current ACMG professional guidelines for the interpretation of germline sequence variants. Interpretations may change over time as more information about the genes in this panel becomes available. Qualified health care providers should be aware that future reclassifications of genetic variants can occur as ACMG guidelines are updated. Factors influencing the quantity and quality of extracted DNA include, but are not limited to, collection technique, the amount of buccal epithelial cells obtained, the patient’s oral hygiene, and the presence of dietary or microbial sources of nucleic acids and nucleases, as well as other interfering substances and matrix-dependent influences. PCR inhibitors, extraneous DNA, and nucleic acid-degrading enzymes may adversely affect assay results.
This laboratory-developed test (LDT) was developed, and its performance characteristics were determined by PreCheck Health Services, Inc. This test was performed at PreCheck Health Services, Inc. (CLIA ID: 10D2210020 and CAP ID: 9101993), which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity testing.
This assay has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Clearance or approval by the FDA is not required for the clinical use of this analytically and clinically validated laboratory-developed test. This assay has been developed for clinical purposes, and it should not be regarded as investigational or for research.
1. American Academy of Ophthalmology Task Force on Genetic Testing (Stone, E. M., Aldave, A. J., Drack, A. V., MacCumber, M. W., Sheffield, V. C., Traboulsi, E., & Weleber, R. G.). (2012). Recommendations for genetic testing of inherited eye diseases: Report of the American Academy of Ophthalmology task force on genetic testing. Ophthalmology, 119(11), 2408–2410.
2. Biesecker, L. G., & Green, R. C. (2014). Diagnostic clinical genome and exome sequencing. New England Journal of Medicine, 370(25), 2418–2425.
3. Britten-Jones, A. C., Gocuk, S. A., Goh, K. L., Huq, A., Edwards, T. L., & Ayton, L. N. (2023). The diagnostic yield of next generation sequencing in inherited retinal diseases: A systematic review and meta-analysis. American Journal of Ophthalmology, 249, 57–73.
4. Burdon, K. P., et al. (2022). Specifications of the ACMG/AMP variant curation guidelines for myocilin: Recommendations from the ClinGen Glaucoma Expert Panel. Human Mutation, 43(10), 1565–1582.
5. Carrigan, M., Duignan, E., Malone, C. P. G., et al. (2016). Panel-based population next-generation sequencing for inherited retinal degenerations. Scientific Reports, 6, 33248.
6. Centers for Disease Control and Prevention. (n.d.). CLIA test complexities. U.S. Department of Health & Human Services.
7. Centers for Medicare & Medicaid Services. (2024–2025). Clinical Laboratory Improvement Amendments (CLIA) program overview and updates. U.S. Department of Health & Human Services.
8. ClinGen Sequence Variant Interpretation (SVI) Working Group. (2025). Variant classification guidance hub. Clinical Genome Resource.
9. Clinical Genome Resource (ClinGen). (2025). Gene–disease validity framework and curation portal. Clinical Genome Resource.
10. College of American Pathologists. (2025). Molecular Pathology Checklist (MM) and NGS best-practice worksheet set (MM09). College of American Pathologists.
11. Congressional Research Service. (2025). FDA’s final rule on laboratory-developed tests (LDTs): Overview and policy considerations. Congressional Research Service.
12. Crooks, K. R., Findeis, S., Karlin-Neumann, G., et al. (2023). Recommendations for next-generation sequencing in molecular pathology. The Journal of Molecular Diagnostics, 25(9), 695–716.
13. Gillespie, R. L., Hall, G., & Black, G. C. (2014). Genetic testing for inherited ocular disease: Delivering on the promise at last? Clinical & Experimental Ophthalmology, 42(1), 65–77.
14. Illumina, Inc. (n.d.). Sequencing technology: Sequencing by synthesis (SBS). Illumina.
15. Landrum, M. J., Lee, J. M., Benson, M., et al. (2018). ClinVar: Improving access to variant interpretations and supporting evidence. Nucleic Acids Research, 46(D1), D1062–D1067.
16. Mustafi, D., Hisama, F. M., Huey, J., & Chao, J. R. (2022). The current state of genetic testing platforms for inherited retinal diseases. Ophthalmology Retina, 6(8), 702–710.
17. Rehm, H. L., Bale, S. J., Bayrak-Toydemir, P., et al. (2013). ACMG clinical laboratory standards for next-generation sequencing. Genetics in Medicine, 15(9), 733–747.
18. Richards, S., Aziz, N., Bale, S., et al. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–424.
19. Riggs, E. R., Andersen, E. F., Cherry, A. M., et al. (2020). Technical standards for the interpretation and reporting of constitutional copy-number variants. Genetics in Medicine, 22(2), 245–257.
20. Roy, S., Coldren, C., Karunamurthy, A., et al. (2018). Standards and guidelines for validating next-generation sequencing bioinformatics pipelines: A joint recommendation of the Association for Molecular Pathology and the College of American Pathologists. The Journal of Molecular Diagnostics, 20(1), 4–27.
21. U.S. Food and Drug Administration. (2024–2025). Laboratory developed tests (LDTs): Final rule and implementation resources. U.S. Food and Drug Administration.
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