DeCure for X-linked intellectual disability-psychosis-macroorchidism syndrome
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for X-linked intellectual disability-psychosis-macroorchidism 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 moduleX-linked intellectual disability-psychosis-macroorchidism 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 x-linked intellectual disability-psychosis-macroorchidism 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
methyl-CpG binding protein 2 (MECP2) — MECP2 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6OGK · 1.65 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
A 2021 case report describes a young female patient with Kleefstra syndrome who presented a first episode of psychosis. The authors note that only a few such cases have been reported, that initial diagnosis wavered, and that there are no recommendations for management. They emphasise the diagnostic and therapeutic complexity of psychiatric comorbidities in Kleefstra syndrome and the need for multidisciplinary care.
A 2015 study identified a novel NLGN4X gene splicing mutation (g.1202C>A) in two brothers with non-syndromic X-linked intellectual disability. The mother was heterozygous with a skewed X inactivation pattern (100%) and was not affected. The mutation was absent in a non-affected daughter. The authors suggest a genotype-phenotype correlation and confirm the efficiency of X exome sequencing for identifying genetic conditions not clinically suspected.
A 2017 review states that X-linked intellectual disability is caused by mutations in roughly 10% of X-chromosome genes, accounting for about 50% of families with XLID. At least 209 different XLID disorders have been described, including 143 syndromic forms. Fragile X syndrome is the most frequent. It is now possible to identify 64% of genetic defects in XLID families with obligate female carriers. The review notes that most mutated genes influence brain development, cell migration, neural network formation and cell-to-cell communication.
What is still missing are prospective studies of psychosis incidence and treatment response in Kleefstra syndrome, functional validation of the NLGN4X splicing mutation, and systematic trials of any drug for the cognitive or psychiatric features of XLID. No drug is mentioned in any of these abstracts. Patient stratification by specific gene mutation and funding for genotype-driven clinical trials remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurocase · 2021 · 6 citations
First episode of psychosis in Kleefstra syndrome: a case report
Abstractgene and characterized by intellectual disability, language disorders, childhood hypotonia and distinct facial features. Only a few cases of first episode of psychosis in KS have already been reported. We describe a young female patient with KS who presented a first episode of psychosis. In a context of an initial diagnosis wavering and a lack of recommendations, this clinical observation illustrates the importance of psychiatric comorbidities and their diagnostic and therapeutic complexity in KS; with a need for multidisciplinary management considering its specific aspects and vulnerabilities.
Greater South Information System · 2015 · 0 citations · open access
Non-Syndromic X Linked Intellectual Disability in Two Brothers with A Novel NLGN4X Gene Splicing Mutation (NC_018934.2: g. 1202C>A)
AbstractX-linked Intellectual Disability (XLID) is an extremely heterogeneous disorder for which many of the causative genes are still unknown.So far, more than one hundred genes of the X chromosome have been found to be altered in males manifesting intellectual disability (ID).NLGN4X is an XLID gene, which has been found, involved in autism and Asperger syndrome involving causative coding mutations.Up to now a few pathological mutations in the promoter and the 5' UTR have been identified.Here we report a non-syndromic X linked Intellectual disability in two brothers with a novel NLGN4X splicing mutation predicted to have a pathogenic effect by the activation of an exonic cryptic acceptor site, with presence of one or more cryptic branch point(s).This mutation g.1202C>A (Genbank accession number NC_018934.2) was identified through X exome sequencing.It was confirmed by Sanger sequencing.The mother was heterozygous with a skewed X inactivation pattern (100%).She is not affected.This variant was predicted to change the splicing process leading to potential alteration of the mRNA.This mutation segregates with the pathological phenotype in all the affected males.However, it was absent in the non-affected daughter, we suggest that it could be in favor of genotype-phenotype correlation.This study also confirms the efficiency of X exome sequencing for identifying specific genetic conditions not clinically suspected.
Encyclopedia of Life Sciences · 2017 · 0 citations
Genetics of <scp>X</scp> ‐Linked Intellectual Disability
AbstractAbstract X‐linked intellectual disability (XLID), formerly called mental retardation , refers to a group of inherited disorders characterised by varying degrees of intellectual disability caused by mutations in various genes present on the X‐chromosome. Deleterious mutations in ∼ 10% of X‐chromosome X genes are implicated in causing XLID disorders in ∼ 50% of families. The remaining XLID genes are expected to be rare and even private to individual families. Historically, XLID is divided into syndromic (IDXS) and nonsyndromic (IDX). At least 209 different XLID disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLID syndrome. It is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. Most of the mutated genes in XLID are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Thus, the diagnosis of intellectual disability in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members. Key Concepts X‐linked intellectual disability (XLID) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation. XLID can be divided into syndromic (MRID) and nonsyndromic (IDX). Genes involved in XLID influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Intellectual disability phenotype can emerge as the final common pathway for many different types of abnormal cellular processing. Genetic counselling is an important part in general management in the case of intellectual disability.
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.
