DeCure for Camptodactyly-tall stature-scoliosis-hearing loss syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for camptodactyly-tall stature-scoliosis-hearing loss syndrome — 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 moduleCamptodactyly-tall stature-scoliosis-hearing loss syndrome 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 camptodactyly-tall stature-scoliosis-hearing loss syndrome 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
fibroblast growth factor receptor 3 (FGFR3) — FGFR3 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 acpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4K33 · 2.3405 Å · ligand PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER (ACP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2016 case, a patient with metatropic dysplasia carried the known lethal TRPV4 mutation L618P as a somatic mosaic, detected by exome sequencing but missed by Sanger sequencing. The mosaic state explained why the phenotype was milder than the perinatal lethal form usually caused by that mutation. No other TRPV4 mutations or treatments were reported.
A 2021 report described a 17-year-old from consanguineous parents with spondylocostal dysostosis type 3 due to a novel homozygous LFNG missense variant c.446C>T, p.(Thr149Ile). The patient had vertebral segmentation defects, rib anomalies, solitary pelvic kidney, uterine dysgenesis (Mayer-Rokitansky-Küster-Hauser syndrome), absence epilepsy, and inner ear deafness. The five previously published SCDO3 patients had only isolated skeletal anomalies or minor non-spine features; the authors proposed the phenotypic spectrum may be broader depending on variant location and nature, but could not exclude a blended phenotype from an undetected additional variant.
A 2024 study of three consanguineous families with brachyolmia and dental anomalies and short stature (DASS) identified LTBP3 variants in seven patients. In Egyptian patients, a novel homozygous splice acceptor variant LTBP3:c.3629-1G>T was found, plus a known homozygous CABP2 missense variant c.590T>C, p.Ile197Thr causing hearing impairment. The hearing loss was thus inherited independently of LTBP3. Pakistani patients carried previously reported homozygous frameshift variants LTBP3:c.132delG and c.2216delG. Additional findings included short webbed neck, broad chest, mild long bone involvement, short distal phalanges, pes planus, and osteopenic bone texture.
A 2021 Chinese review summarised that sensorineural hearing loss and scoliosis co-occur in hereditary connective tissue syndromes, hereditary motor and sensory neuropathies, lysosomal storage disorders, and endocrine diseases, with significant phenotypic and genetic heterogeneity. No specific drug or treatment was discussed. What remains missing for any of these syndromes is a targeted therapy, a clinical trial, and systematic patient stratification by genotype and phenotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2016 · 14 citations · open access
Somatic mosaicism for a lethal <i>TRPV4</i> mutation results in non‐lethal metatropic dysplasia
Clinical Genetics · 2021 · 4 citations · open access
Clinical and molecular delineation of spondylocostal dysostosis type 3
AbstractSpondylocostal dysostosis (SCDO) is a heterogeneous group of rare spine disorders defined by multiple vertebral segmentation defects (M-SDV) and rib anomalies. Patients with SCDO present with short trunk short stature and mild to significant scoliosis. Severely reduced thorax size and a loss of natural thoracic kyphosis might lead to respiratory insufficiency in some affected individuals. Seven subtypes are differentiated based on the affected gene, including SCDO3 associated with autosomal recessive pathogenic variants in LFNG. LFNG belongs to the Fringe genes encoding a family of glycosyltransferases in the Notch signaling pathway and is localized to the Golgi. The Notch pathway is essential throughout embryonic development and regulates somite formation.1 To date five patients with frameshift or missense variants in LFNG gene presenting with M-SDV were published.1-4 Two individuals showed further minor nonspine-related anomalies (hernia, camptodactyly), but no major organ involvement has been described in SCDO3 patients so far. We report a 17-year-old individual from healthy consanguineous parents with generalized vertebral segmentation defects, rib anomalies and further nonskeletal findings (Figure 1(A)–(D)). In WES, we identified a homozygous missense variant c.446C>T, p.(Thr149Ile) in LFNG, not previously described in SCDO3 patients or genetic databases (Figure 1(E)). The variant was predicted to impair protein function in Notch signaling, a mechanism previously described (Figure 1(F),(G)). Although the five previously reported cases had isolated skeletal anomalies or minor nonspine-related features, here the reported individual presented with various additional anomalies including solitary pelvic kidney, uterine dysgenesis mayer-rokitansky-küster-hauser syndrome, absence epilepsy, and inner ear deafness. A part of these anomalies could also be attributed to the MURCS association (MUllerian duct aplasia, unilateral Renal agenesis, Cervicothoracic Somite anomalies).5 As no other genetic variants were identified, neither in the exome nor in chromosomal microarray analysis, we propose that the phenotypic spectrum of this syndrome can be much broader, perhaps depending on the localization and nature of the affected variant, although we cannot exclude a blended phenotype due to an undetected additional variant. Identification of additional individuals with mutations in LFNG will help to clarify the phenotypic spectrum of SCDO3. We thank all participants and their families for taking part in this study. We also thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. This study was supported by grants from the German Research Foundation (DFG; grants TH 896/3-4 and TH 896/7-1) to Christian T. Thiel. The study was approved by the ethics committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Informed consent was obtained from the patient and her parents. The authors declare no potential conflict of interest. The peer review history for this article is available at https://publons.com/publon/10.1111/cge.13952. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
[Advances in studies on genetics of syndromes combining sensorineural hearing loss with scoliosis].
AbstractSensorineural hearing loss and scoliosis are common in several disease groups, such as hereditary connective tissue syndrome, hereditary motor and sensory neuropathy, lysosomal storage syndrome and endocrine disorders. These diseases have significant phenotypic diversity and genetic heterogeneity, different subtypes show inconsistent characteristics of deafness. Moreover, subtypes with similar clinical manifestations have different genetic mechanisms. Using new generation sequencing technology, considerable progress has been achieved in these diseases. This paper reviews clinical manifestations and genetic mechanism of syndromes combining sensorineural hearing loss and scoliosis.
Greater South Information System · 2024 · 0 citations · open access
Brachyolmia, dental anomalies and short stature (DASS): Phenotype and genotype analyses of Egyptian and Pakistani patients
AbstractAbstract Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the LTBP3 gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (LTBP3:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (CABP2: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (LTBP3:c.132delG; p.Pro45Argfs*25) and (LTBP3:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of LTBP3 in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of LTBP3. We are reporting LTBP3 variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of LTBP3.
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.
