DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for trichorhinophalangeal syndrome type II — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTrichorhinophalangeal syndrome type II maps to a 2-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 trichorhinophalangeal syndrome type ii 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
exostosin glycosyltransferase 1 (EXT1) — EXT1 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 udpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7SCK · 2.8 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
Trichorhinophalangeal syndrome type II is a contiguous gene syndrome caused by a de novo deletion of the two contiguous EXT1 and TRPS1 genes at chromosome 8q24.1. It combines the clinical features of trichorhinophalangeal syndrome type I with mental retardation and hereditary multiple exostoses. In a Turkish cohort of 22 patients, 3 had type II and all had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. Two of those 3 patients had severe intellectual disability, and the 3 patients with the EXT1 deletion beginning from exon 2 had exostoses. Microdeletion sizes did not correlate with facial or skeletal features, but patients with larger deletions had severe intellectual disability.
All patients in that cohort, across both types, shared typical craniofacial findings such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in type I and type II, 3 of 19 type I patients had mild intellectual disability, whereas 2 of 3 type II patients had severe intellectual disability. The type II patients also had exostoses. No drug treatment is mentioned in any of the abstracts.
No clinical trial, no drug intervention, and no repurposing candidate are reported for trichorhinophalangeal syndrome type II. What is missing is any funded effort to identify molecular targets, any preclinical model work, and any patient stratification beyond deletion size. Without these, the condition remains a purely descriptive genetic diagnosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 2008 · 8 citations
A novel missense mutation in the<i>TRPS1</i>gene underlies trichorhinophalangeal syndrome type III
AbstractConflicts of interest: none declared. Trichorhinophalangeal syndrome (TRPS) is a dominantly inherited condition characterized by developmental defects of hair, face and selected bones. Three different clinical forms of TRPS are known: type I (TRPS I), type II (TRPS II) and type III (TRPS III). These share some major clinical features such as slow‐growing hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone‐shaped epiphyses at the phalanges, hip malformations, and short stature.1, 2 TRPS III (Sugio–Kajii syndrome) is associated with severe brachydactyly and short stature resulting from the progressing shortening of all the phalanges and metacarpals and some long bones.2 Several studies have implicated mutations in the TRPS1 gene at chromosome 8q24.11 as the underlying cause of TRPS I and TRPS III. Several deletions, nonsense and missense mutations causing TRPS I have been identified in the entire coding region of the TRPS1 gene.1–7 Mutations causing TRPS III are located solely in exon 6 of the TRPS1 gene,2, 3 which affect the function of the zinc‐finger domain of TRPS1 protein. TRPS II (Langer–Giedion syndrome) is a contiguous gene syndrome combining the clinical features of TRPS I and mental retardation, and hereditary multiple exostoses due to a de novo deletion of the two contiguous EXT1 and TRPS1 genes at chromosome 8q24.1.8
Turkish Archives of Pediatrics · 2023 · 4 citations · open access
The Clinical and Molecular Spectrum of Trichorhinophalangeal Syndrome Types I and II in a Turkish Cohort Involving 22 Patients
AbstractOBJECTIVE: Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. MATERIALS AND METHODS: A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. RESULTS: A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability. CONCLUSION: This study has expanded the existing knowledge on the phenotype-genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.
Zeitschrift für Orthopädie und ihre Grenzgebiete · 2008 · 1 citations
Hand- und Fußdeformitäten bei einem Trichorhinophalangeal-Syndrom Typ I
AbstractThe trichorhinophalangeal syndrome type I is a rare, probably autosomal-dominant inherited disorder, characterized by anomalies of the cranium and face, hair, skeleton and soft parts of the hands and the feet. Typical deformities of the syndrome in hands and feet (e.g. brachydactylie, deviation and curvature of fingers and toes due to cone-shaped joints) are explained by description of the findings in three adult members of a family.
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.
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