DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Treacher Collins syndrome 1 — 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 moduleTreacher Collins syndrome 1 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 treacher collins syndrome 1 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
transglutaminase 1 (TGM1) — TGM1 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 2XZZ · 2.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Treacher Collins syndrome is an autosomal dominant craniofacial disorder with an estimated incidence of 1 in 50,000 live births, and 60% of cases result from sporadic mutations. The gene TCOF1, which encodes the protein treacle, was mapped in 1996. Mutation screening studies have found that the majority of pathogenic mutations are small deletions and insertions causing frameshifts predicted to produce a truncated protein. About 70% of recognised TCOF1 mutations are deletions. A commonly occurring 5 bp deletion in exon 24 is found in approximately 16% of families, but most mutations are family specific. More than 50% of all described pathogenic mutations cluster in five exons (10, 15, 16, 23, and 24), which are considered mutational hot spots. There is no correlation between the type or location of the mutation and the phenotypic expression. A heterozygous insertion c.2013_2014insG causing premature termination at 680 amino acids has been described in one patient. TCS can also be caused by mutations in POLR1C, POLR1D, or POLR1B genes.
A lateral cephalometric study of 20 unoperated TCS patients aged 5 to 17 years (mean 8.8 years) compared to age-matched and sex-matched controls found decreased anterior, posterior, and total cranial base lengths, a reduced cranial base angle, and a deficient maxilla positioned posteriorly. Anterior and posterior facial heights were decreased, lower face height was increased, and total face height was decreased. The mandible was characteristically small in body length and total mandibular length, with deficient maximum ramus width, increased mandibular plane angle and gonial angle, and retropositioning. The maxillary and functional occlusal planes were tipped upwards posteriorly. These measurements provide a skeletal basis for the hallmark clinical findings.
A narrative review of literature from 2010 to 2024, drawing on 23 publications from 116 identified articles, describes TCS as a genetic disorder affecting facial structures with variable clinical manifestations that impact quality of life. Microtia and conductive hearing loss are otology manifestations. Diagnosis is based on clinical manifestations along with genetic confirmation. The review emphasises that early identification and diagnosis are crucial for planning management and interventions.
What remains missing is any pharmacological or molecular treatment for the underlying condition. No drug intervention is described in any of these abstracts. The research is limited to genetic characterisation, cephalometric description, and clinical diagnosis. There is no trial design, no patient stratification strategy, and no funding directed toward a therapy. The functional role of treacle remains unknown, and no animal model or repurposing screen is reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 2002 · 65 citations · open access
Screening of <i>TCOF1</i> in patients from different populations: confirmation of mutational hot spots and identification of a novel missense mutation that suggests an important functional domain in the protein treacle
AbstractTreacher Collins syndrome (TCS, MIM *154500) is an autosomal dominant craniofacial disorder characterised by malar hypoplasia, micrognathia, downward slanting palpebral fissures, lower eyelid coloboma, malformed auricles, conductive deafness, and cleft palate. The estimated incidence is 1/50 000, with 60% of the cases resulting from sporadic mutations.1 There is marked phenotypic variability among patients, ranging from perinatal death because of a compromised airway to those that go undetected by medical examination. The gene underlying this condition, TCOF1 , was mapped in 19962 and since then mutation detection studies have concluded that: (1) the majority of pathogenic mutations are small deletions and insertions causing frameshifts that are predicted to result in a truncated protein; (2) mutations (both polymorphic and pathogenic) can be found throughout the 25 coding exons of the gene; (3) most mutations are family specific with the exception of a commonly occurring 5 bp deletion in exon 24 (found in approximately 16% of families); and (4) there is no correlation between type and/or localisation of the mutation and phenotypic expression.3–6 Furthermore, the observation that more than 50% of all described pathogenic mutations known to date are clustered in five exons (10, 15, 16, 23, and 24) has led to the hypothesis that these five exons are mutational hot spots, suggesting that any effort to identify mutations in TCOF1 would benefit from testing these five exons before extending the analysis to the rest of the gene.6
The protein encoded by the TCOF1 gene, treacle, has repetitive motifs encoded by exons 7-16, which are subject to phosphorylation by casein kinase II7 and a nucleolar localisation signal on its C-terminus.8 It bears weak similarity to a family of nucleolar phosphoproteins and its precise function remains unknown.9,10 In the present work, screening for TCOF1 mutations …
Journal of Craniofacial Surgery · 2013 · 36 citations
Cephalometric Assessment of Craniofacial Morphology in Patients With Treacher Collins Syndrome
AbstractBACKGROUND AND PURPOSE: Treacher Collins syndrome is an autosomal dominant craniofacial disorder affecting derivatives of the first and second branchial arches. Given the conflicting reports in the literature regarding the extent of anterior-posterior and vertical (superior-inferior) dysplasia of the cranial base, maxilla, and mandible, this study was designed to provide a comprehensive lateral cephalometric assessment of the craniofacial morphology of unoperated patients with Treacher Collins syndrome. METHODS: The records of 45 patients with Treacher Collins syndrome registered at the Institute of Reconstructive Plastic Surgery of the NYU Langone Medical Center from the period of 1975 to 2008 were reviewed. Inclusion criteria included (1) patients between with the ages of 5 and 17 years, (2) no history of prior surgical intervention to correct skeletal deformity, and (3) diagnostic quality lateral cephalograms. Twenty patients satisfied the inclusion criteria with 12 male and 8 female patients in the sample and a mean age at the time of the lateral cephalogram of 8.8 years (range 5.2 to 16.7 years). Thirty angular and linear variables were measured to assess anterior-posterior and vertical (superior-inferior) position of the cranial base, maxilla, and mandible. Each patient's measurements were compared to age-matched and sex-matched control samples derived from the Moyers growth studies. The mean and standard deviation for each variable was then determined. RESULTS: Lateral cephalometric analysis showed decreased anterior, posterior, and total cranial base lengths and a reduced cranial base angle. The anteroposterior dimension or length of the maxilla is deficient and the maxilla is positioned posteriorly with respect to the cranial base. Both anterior and posterior facial heights (superior-inferior dimension) are decreased. Lower face height is increased, whereas total face is decreased. The maxillary and functional occlusal planes are tipped upwards posteriorly. The mandibular morphology is characteristically small in both body length and total mandibular length, and the maximum ramus width is also deficient. The mandibular plane angle and gonial angle are increased. The mandible is retropositioned. CONCLUSIONS: A lateral cephalometric analysis is described that provides a skeletal basis for the hallmark clinical findings associated with Treacher Collins syndrome. This is of importance because an understanding of the underlying skeletal dysmorphology may shed light on the etiology and growth pattern, and impacts the overall treatment planning for skeletal correction.
Acta fytotechnica et zootechnica/Acta fytotechnica et zootechnica · 2016 · 0 citations · open access
Mutation in exon 13 of the TCOF1 gene in patient with Treacher Collins syndrome
AbstractTreacher Collins Syndrome (TCS) is associated with an abnormal differentiation of the first and the second pharyngeal arch during fetal development. This causes mostly craniofacial deformities, which require numerous corrective surgeries. TCS is an autosomal dominant disorder and it occurs in general population with the frequency of in 1 in 50,000 live births. TCS is caused by mutations in the TCOF1 gene. This gene encodes the serine/alanine-rich protein named Treacle. TCS can also be caused by mutations in the POLR1C and POLR1D genes. About 70% of recognized mutations of the TCOF1 gene are deletions, which lead to a frame shift, formation of termination codon and shortening of the protein product of the gene. A heterozygous insertion c.2013_2014insG was described in one patient with TCS. The insertion causes premature termination of translation at 680aa.
MICROTIA IN TREACHER COLLINS SYNDROME: A REVIEW ARTICLE
AbstractIntroduction: Treacher Collins Syndrome (TCS) is a condition affecting the development of facial structures. TCS presents with variable clinical manifestations and can impact the quality of life of those affected. Early identification and diagnosis are crucial management planning and intervention. Objective: To understand the embryology, genetic abnormalities, and manifestations of TCS which would facilitate the diagnosis. Methods: A narrative review of the literature published between 2010 and 2024. The literature search was conducted using the keywords "Treacher Collins Syndrome" and related terms (embryology, epidemiology, diagnosis) across academic databases such as PubMed, Google Scholar, and ScienceDirect. Result: From the 116 articles identified, a review was conducted on 23 publications deemed relevant and appropriate to the topic. Treacher Collins Syndrome (TCS), also known as Mandibulofacial Dysostosis, is a genetic disorder affecting facial structures, characterized by variable clinical manifestations. TCS has impact on the quality of life of those affected. It is inherited in an autosomal dominant manner and involves mutations in the TCOF1, POLR1D, POLR1C or POLR1B genes, which disrupts the development of the pharyngeal arches during embryogenesis. Microtia and conductive hearing loss are otology manifestations of TCS. TCS is diagnosed based on clinical manifestations, along with genetic confirmation. Conclusion: Identification and diagnosis of Treacher Collins Syndrome (TCS) are crucial for planning management and interventions that can improve the patient's quality of life. Keywords: microtia, Treacher Collins syndrome, mandibulofacial dysostosis, conductive hearing los
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.
