DeCure for Autosomal recessive dyskeratosis congenita 4
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for autosomal recessive dyskeratosis congenita 4 — 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 moduleAutosomal recessive dyskeratosis congenita 4 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 autosomal recessive dyskeratosis congenita 4 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
telomerase reverse transcriptase (TERT) — TERT 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…
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RCSB Protein Data Bank · entry 9Q16 · 2.7 Å · ligand 2'-deoxy-5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]guanosine (XG4). Experimental structure, not a prediction.
What the evidence adds up to
Dyskeratosis congenita is a rare hereditary disease with an estimated annual incidence of 1 in 1 million individuals, occurring predominantly in males at a ratio of approximately 10:1. The classic clinical triad consists of reticulate hyperpigmentation, nail dystrophy and leukoplakia, with at least one of these signs present in around 80–90% of cases. Bone marrow failure is the leading cause of death, and other lethal complications include pulmonary disease and malignancy. Mutations in 19 genes are associated with the disorder; a fifth of pathogenic mutations are found in DKC1, the gene coding for dyskerin. Three modes of inheritance are recognised: X-linked recessive, autosomal dominant and autosomal recessive. Eight genes (DKC1, TERC, TERT, NOP10, NHP2, TINF2, TCAB1 and RTEL1) account for approximately 60% of all cases.
A 1993 linkage study of three families with X-linked recessive dyskeratosis congenita reported a combined maximum lod score of 2.00 at zero recombination with marker DXS52 on Xq28, bringing the reported maximum lod score for the X-linked gene and DXS52 to 5.33 at zero recombination fraction. A 2002 report described two male patients in a Japanese kindred with a novel missense mutation L398P in the DKC1 gene. Despite sharing the same mutation, one patient had significantly milder haematological symptoms than the other, indicating that other factors influence disease severity. A 2020 case report described a two-year-old female who presented the cardinal signs and symptoms at an early age.
A 2013 case report described a 43-year-old female never-smoker with a TINF2 gene mutation who presented with cough, progressive dyspnoea and pulmonary fibrosis. This was the first reported dyskeratosis congenita patient with pulmonary fibrosis carrying a TINF2 mutation. Mutations in TERC, TERT and DKC1 had previously been associated with familial and idiopathic pulmonary fibrosis, but the relationship between other dyskeratosis congenita genes and pulmonary fibrosis had not been clarified. A 2020 literature review notes that the main causes of mortality are bone marrow failure, pulmonary disease and malignancy, but does not report any specific treatment outcomes or survival data for any drug.
What is still missing: no clinical trial data exist for any drug in autosomal recessive dyskeratosis congenita 4 specifically. The literature consists entirely of case reports and genetic linkage studies. No randomised controlled trials, no prospective treatment cohorts, and no validated biomarkers for stratifying patients by disease severity or progression risk have been reported. Funding for natural history studies and multi-centre registries would be needed before any drug could be tested in this ultra-rare population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JDDG Journal der Deutschen Dermatologischen Gesellschaft · 2020 · 63 citations
Dyskeratosis congenita: a literature review
AbstractDyskeratosis congenita is a rare hereditary disease that occurs predominantly in males and manifests clinically as the classic triad of reticulate hyperpigmentation, nail dystrophy and leukoplakia. It increases the risk of malignancy and other potentially lethal complications such as bone marrow failure, lung and liver diseases. Mutations in 19 genes are associated with dyskeratosis congenita, and a fifth of the pathogenic mutations are found in DKC1, the gene coding for dyskerin. This review aims to address the clinical and genetic aspects of the disease.
European Respiratory Journal · 2013 · 56 citations · open access
Pulmonary fibrosis in dyskeratosis congenita with<i>TINF2</i>gene mutation
AbstractTo the Editor:
Dyskeratosis congenita is a rare inherited disorder of ectodermal dysplasia characterised by the classical mucocutaneous triad of abnormal skin pigmentation, nail dystrophy and leukoplakia [1–3], at least one of which is present in around 80–90% of dyskeratosis congenita cases. Bone marrow failure is another common feature, and a variety of other abnormalities ( e.g. dental, gastrointestinal, neurological, ophthalmic, pulmonary and skeletal) have been also described [1–3]. The main causes of mortality in dyskeratosis congenita are bone marrow failure, pulmonary disease and malignancy [1]. Three modes of inheritance have been recognised: X-linked recessive, autosomal dominant and autosomal recessive [1, 3]. Eight dyskeratosis congenita genes ( DKC1 (dyskeratosis congenita 1), TERC (telomerase RNA component), TERT (telomerase reverse transcriptase), NOP10 (nucleolar protein 10), NHP2 , TINF2 (TERF1-interacting nuclear factor 2), TCAB1 and RTEL1 (regulation of telomere elongation helicase 1)) have already been identified, and their mutations account for ∼60% of all dyskeratosis congenita cases [1]. Among the dyskeratosis congenita genes, mutations in TERC , TERT and DKC1 have recently been reported to be associated with familial pulmonary fibrosis and idiopathic pulmonary fibrosis, and pulmonary fibrosis is recognised as one of the features of dyskeratosis congenita. However, the relationship between mutations in the other dyskeratosis congenita genes and pulmonary fibrosis has not yet been clarified. To the best of our knowledge, this is the first case report describing a dyskeratosis congenita patient with pulmonary fibrosis who had a TINF2 mutation.
A 43-year-old female visited our hospital with cough and progressive dyspnoea. She had never smoked, and had a …
Journal of Medical Genetics · 1993 · 36 citations · open access
Dyskeratosis congenita: three additional families show linkage to a locus in Xq28.
AbstractDyskeratosis congenita (DC) is a rare inherited disorder with most families being of the X linked recessive type. We describe three families which show linkage to the marker DXS52 on Xq28. The combined maximum lod score was 2.00 at zero recombination. This is further evidence that the X linked DC gene is located at Xq28 and brings the reported maximum lod score for DC and DXS52 to 5.33 at zero recombination fraction, with a supporting recombination fraction interval of 0.00-0.10.
Pediatric Hematology and Oncology · 2002 · 20 citations
A NOVEL MISSENSE MUTATION IN THE DKC1 GENE IN A JAPANESE FAMILY WITH X-LINKED DYSKERATOSIS CONGENITA
AbstractThe authors report 2 male patients with dyskeratosis congenita (DC) in a Japanese kindred. Sequencing of the complementary DNA of the dyskerin gene (DKC1) revealed a T-to-C transition at nucleotide 1285 in exon 12 that resulted in a novel missense mutation L398P. Despite harboring the same mutation in the DKC1 gene, one patient had significantly milder hematological symptoms than the other, indicating that there may be other factors that determine the severity of DC.
Journal of the Portuguese Society of Dermatology and Venereology · 2020 · 0 citations · open access
Dyskeratosis Congenita and Short Telomeres in a Female Patient
AbstractDyskeratosis Congenita (DC) is a hereditary and multisystemic syndrome, with heterogeneous clinical and genetic manifestations, characterized as a disease associated with maintenance of defects and early telomere shortening. It is a rare condition, with an estimated annual incidence of 1 in 1 million individuals, and is more common in males than females, with an approximate ratio of 10:1. The main initial clinical manifestations are disorders of cutaneous pigmentation, nail dystrophy and abnormalities in the oropharynx, usually occurring between five and twelve years of age. Bone marrow failure (BMF) is the leading cause of death related to this disease. We present a case report of a child, female, two years old, who presented the cardinal signs and symptoms of DC at an early age, and we emphasize the importance of multidisciplinary monitoring of the patient.
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.
