DeCure for Syndromic X-linked intellectual disability Shashi type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability Shashi type — 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 moduleSyndromic X-linked intellectual disability Shashi type 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 syndromic x-linked intellectual disability shashi type 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
CCCTC-binding factor (CTCF) — CTCF 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7W1M · 6.5 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
A 2015 report describes a 17-year-old female with a de novo KIAA2022 nonsense mutation who had short stature, microcephaly, severe intellectual disability, poor speech, epilepsy, and autistic behaviour. Her X-inactivation pattern was normal, which the authors state suggests the mutation is causing the phenotype. This case contests the previous view that KIAA2022 mutations only affect males.
A 2017 study of a family with a novel DLG3 mutation found that the 12-year-old male index patient had moderate intellectual disability and dysmorphic features. Four female relatives also carried the mutation. One maternal aunt had moderate intellectual disability and significantly skewed X-inactivation that favoured inactivating the normal DLG3 allele. The proband’s healthy mother had skewed X-inactivation in the opposite direction, inactivating the mutated allele. Two other female relatives had intermediate cognitive phenotypes and random X-inactivation. The authors conclude that heterozygous female mutation carriers can be as severely affected as males.
A 2023 case study reports two patients from one Korean family with deletions of exons 1 and 2 of the OPHN1 gene. The authors note that OPHN1-associated X-linked intellectual disability commonly includes mental retardation and cerebellar hypoplasia, with possible additional features such as epilepsy, ataxia, strabismus, urogenital abnormality, facial dysmorphism, and ventriculomegaly.
What is missing across these reports is any systematic attempt to predict which female carriers will be symptomatic, any prospective trial of interventions, and any patient stratification beyond X-inactivation skewing. No drug is mentioned in any of the abstracts.
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 · 2015 · 28 citations
<i>KIAA2022</i> nonsense mutation in a symptomatic female
AbstractMutations in the KIAA2022 gene have been implicated in non-syndromic X-linked intellectual disability. Thus far, all carrier females reported have been unaffected and genotype-phenotype correlations have not been described. Herein, we report a de novo KIAA2022 nonsense mutation in a 17-year-old female with short stature, microcephaly, severe intellectual disability, poor speech, epilepsy, and autistic behavior. X-inactivation pattern is normal suggesting that the mutation is causing the phenotype. This report contests the current view that KIAA2022 mutations only affect males, which has implications for testing and genetic counseling.
American Journal of Medical Genetics Part A · 2017 · 17 citations
Skewed X‐inactivation in a family with <i>DLG3‐</i>associated X‐linked intellectual disability
AbstractMutations in DLG3 are a rare cause of non-syndromic X-linked intellectual disability (XLID) (MRX90, OMIM *300189). Only ten DLG3 mutations have been reported to date. The majority of female heterozygous mutation carriers was healthy and had random X-inactivation patterns. We report on an XLID family with a novel DLG3 mutation. The 12-year-old male index patient had moderate intellectual disability (ID) and dysmorphic features. The mutation was also present in four female relatives. A maternal aunt had moderate ID and significantly skewed X-inactivation favorably inactivating the normal DLG3 allele. The proband's healthy mother also had skewed X-inactivation but in the opposite direction (i.e., inactivation of the mutated allele). Two other female relatives had intermediate cognitive phenotypes and random X-inactivation. This family broadens the mutational and phenotypical spectrum of DLG3-associated XLID and demonstrates that heterozygous female mutation carriers can be as severely affected as males. Reports of additional families will be needed to elucidate the causes of unfavorable skewing in female XLID patients.
Laboratory Medicine Online · 2023 · 0 citations · open access
The First Cases of <i>OPHN1</i> Exons 1 and 2 Deletion in Two X-linked Intellectual Developmental Disorder Patients in Korea
Abstractseveral case reports of wide spectrums of X-linked intellectual disabilities (XLIDs) associated with variants of the OPHN1 gene.[2-9].XLIDs caused by OPHN1 gene mutations have mental retardation and cerebellar hypoplasia in common, and other features such as epilepsy, ataxia, strabismus, urogenital abnormality, facial dysmorphism, and ventriculomegaly can also be observed.In this case study, we report two cases of OPHN1-associated XLID found in one family, the rst to our knowledge, in Korea.
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.
