DeCure for Exudative vitreoretinopathy 2, X-linked
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for exudative vitreoretinopathy 2, X-linked — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleExudative vitreoretinopathy 2, X-linked maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for exudative vitreoretinopathy 2, x-linked is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
norrin cystine knot growth factor NDP (NDP) — NDP is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5BQ8 · 2.0 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Familial exudative vitreoretinopathy has three clinical stages and is slowly progressive, according to a 1971 report of a family with autosomal dominant inheritance. Four patients in stage 2 were treated with cryopexy to prevent progression to stage 3, where macular vision is lost. Pathologic findings in two patients from 1981 showed a prominent vitreous membrane posterior to the ora serrata, with multiple secondary changes in the retina and anterior segment not previously described.
X-linked exudative vitreoretinopathy in a four-generation family presented as abnormal vascularisation at birth, resembling retinopathy of prematurity, retinal folds, or advanced enophthalmos or phthisis. Linkage analysis in seven affected males and five obligate carrier females suggested a gene locus at Xq21.3 or Xp11, the latter including the Norrie disease gene. Four novel missense mutations in the Norrie disease gene (R41K, H42R, K58N, Y120C) were identified in one X-linked and four sporadic cases of FEVR in a 1997 study; the H42R mutation segregated with disease across three generations, and none of the alterations were found in 17 unaffected family members or 36 random controls.
A 2014 study of a large consanguineous kindred with autosomal recessive inheritance found a novel TSPAN12 mutation (c.542G>T, p.C181F) segregating with ocular disease. Affected individuals showed variable phenotypes consistent with FEVR, persistent fetal vasculature, and Norrie disease, suggesting these conditions form a spectrum with clinical and genetic overlap caused by mutations in genes of the Norrin/β-catenin signalling pathway. A separate 1997 case of bilateral tractional retinal detachments with peripheral fibrovascular proliferation simulating FEVR occurred in a child with cutis marmorata telangiectatica congenita; after vitrectomy both posterior poles were reattached, but no Norrie disease gene abnormalities were found.
What remains missing is a clear understanding of why identical mutations produce such variable phenotypes within families, and whether this variability depends on timing of the insult, additional genetic modifiers, or environmental factors. No controlled trial of any treatment has been reported; cryopexy was described in only four patients without long-term outcome data, and vitrectomy was reported in a single case of a related condition. Patient stratification by genotype and stage, prospective natural history studies, and funding for multicentre trials are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Ophthalmology · 1971 · 137 citations
Familial Exudative Vitreoretinopathy
AbstractA family with exudative vitreoretinopathy displayed findings similar to earlier reported cases of this disease and enabled us to expand the original observations. The disease appears to have three clinical stages and is slowly progressive. This family exhibits an autosomal dominant hereditary pattern. Four patients in stage 2 were treated with cryopexy to prevent progression of the disease to stage 3 where macular vision is lost. Early examination is stressed in suspected individuals.
Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of Familial Exudative Vitreoretinopathy
AbstractX-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.
British Journal of Ophthalmology · 1993 · 59 citations · open access
X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.
AbstractA four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.
Pathologic Findings in Familial Exudative Vitreoretinopathy
Abstract• Two patients with familial exudative vitreoretinopathy were seen by us, and the clinical features of their condition are reviewed herein. The pathologic findings of both patients showed a prominent vitreous membrane posterior to the ora serrata. To our knowledge, this finding, as well as multiple secondary changes in the retina and the anterior segment, has not been previously described.
American Journal of Medical Genetics Part A · 2014 · 21 citations
Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra‐familial phenotypic variability
AbstractDevelopmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway.
OCULAR FINDINGS IN CUTIS MARMORATA TELANGIECTATICA CONGENITA
AbstractBACKGROUND: Cutis marmorata telangiectatica congenita is a rare, cutaneous, reticulated, vascular anomaly characterized by congenital persistent cutis marmorata, telangiectasis, and phlebectasis. While systemic abnormalities frequently are associated with cutis marmorata telangiectatica congenita, ophthalmic abnormalities are quite rare and include congenital glaucoma and congenital, bilateral, total retinal detachments with secondary glaucoma. METHODS: The authors report a case of bilateral, tractional retinal detachments associated with peripheral fibrovascular proliferation simulating familial exudative vitreoretinopathy in a female child with cutis marmorata telangiectatica congenita. Molecular genetic analysis of the Norrie's disease gene was performed. RESULTS: After vitrectomy, the posterior poles of both eyes were reattached successfully. No abnormalities of the Norrie's disease gene were identified. CONCLUSIONS: Bilateral exudative vitreoretinopathy is a rare ophthalmic manifestation associated with cutis marmorata telangiectatica congenita.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
