DeCure for Intellectual disability, autosomal recessive 60
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal recessive 60 — 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 moduleIntellectual disability, autosomal recessive 60 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 intellectual disability, autosomal recessive 60 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.
What the evidence adds up to
A missense mutation in MED23 (p.R617Q) was found to cosegregate with nonsyndromic autosomal recessive intellectual disability in one family. The mutation impaired the response of JUN and FOS immediate early genes to serum mitogens by altering the interaction between enhancer-bound transcription factors and Mediator. Transcriptional dysregulation of these genes was also seen in cells from patients with other neurological disorders linked to mutations in other Mediator subunits or interacting proteins. The authors suggested that altered immediate early gene expression might be a common molecular hallmark of cognitive deficit, but this remains a suggestion from a single-family study.
A separate report described a three-year-old girl with intellectual disability, speech delay, and developmental delays who carried a homozygous 1.16 megabase microdeletion at 8p22 that included the entire TUSC3 gene. This was the first such case reported from Turkey. The authors noted that microarray techniques can help clinicians when the differential diagnosis is broad, but no treatment or intervention was tested.
A 2021 case report identified a de novo heterozygous nonsense variant in TRIP12 (c.40C>T, p.Arg14X) in a patient with intellectual disability. The variant was classified as pathogenic under ACMG criteria. This is an autosomal dominant form, not autosomal recessive, and no drug or therapy was investigated.
A 2021 review of autosomal recessive intellectual disability noted that most cohort genetic studies have emphasised de novo variants, but that autosomal recessive forms account for most cases in inbred populations. The review discussed clinical and molecular aspects but did not report any therapeutic trials or drug repurposing data. What is still missing for autosomal recessive intellectual disability 60 specifically is any clinical trial, any drug tested in patients, any patient stratification beyond single families, and any funding directed toward a repurposing strategy for this particular gene.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science · 2011 · 118 citations
<i>MED23</i> Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene Expression
AbstractMED23 is a subunit of the Mediator complex, a key regulator of protein-coding gene expression. Here, we report a missense mutation (p. R617Q) in MED23 that cosegregates with nonsyndromic autosomal recessive intellectual disability. This mutation specifically impaired the response of JUN and FOS immediate early genes (IEGs) to serum mitogens by altering the interaction between enhancer-bound transcription factors (TCF4 and ELK1, respectively) and Mediator. Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurological disorders linked to mutations in other Mediator subunits or proteins interacting with MED. These findings highlight the crucial role of Mediator in brain development and functioning and suggest that altered IEG expression might be a common molecular hallmark of cognitive deficit.
A Homozygous 1.16 Megabases Microdeletion at 8p22 Including The Whole TUSC3 in A Three Years Old Girl with Intellectual Disability and Speech Delay.
AbstractIntellectual disability (ID) is defined as an intelligence quotient (IQ) level below than 70. In the present paper, a 1.16 megabases (Mb) homozygous deletion in the 8p22 region was identified in a three years old girl with ID, speech and developmental delays. This is the first report from Turkey with this form of ID. The present paper demonstrates that application of microarray technique to help clinicians, especially when clinical diagnosis includes a complex group of disorders (such as ID) and differential diagnostic list is broad.
[Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient].
AbstractOBJECTIVE: To explore the genetic basis for a patient with intellectual disability. METHODS: Whole exome sequencing and Sanger sequencing were carried out for the patient. The result was verified in her family. RESULTS: DNA sequencing revealed that the patient has carried a heterozygous nonsense c.40C>T (p.Arg14X) variant of the TRIP12 gene, which was de novo in origin. The variant was unrecorded in the Human Gene Mutation Database. Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+ PS2+ PP3). CONCLUSION: The patient was diagnosed with autosomal dominant intellectual disability due to heterozygous c.40C>T variant of the TRIP12 gene.
Majmaah Journal of Health Sciences · 2021 · 0 citations · open access
Review On Clinical And Molecular Genetics Of Autosomal Recessive Intellectual Disability
AbstractIntellectual disability (ID) is a relatively common phenotype with multiple etiologies. Recent progress in the genetics of ID greatly expanded our understanding of the biological defects underlying this clinical entity. While most published cohort genetic studies on ID revealed the important contribution of de novo (germline or postzygotic) variants, we focused in this study of autosomal recessive ID (ARID), that account for most of the molecular bases in ID cases in inbred populations. We discussed the current state of ARID from a clinical, molecular and genetics standpoints.
Biallelic Variant in <scp> <i>SLC6A17</i> </scp> in a Pakistani Family With Autosomal Recessive Intellectual Disability
AbstractAutosomal recessive intellectual disability affects 1%-3% of the general population and is a major concern in countries where consanguineous marriages are common. Mental retardation autosomal recessive 48 (MRT 48) (OMIM 616269) is a recessive syndromic disorder characterized by progressive tremors, speech impairment, and behavioral problems. In the present study, we highlight a family with a case of MRT 48. The index patient was second born to healthy consanguineous parents with a history of intellectual disability. Whole exome sequencing of the patient was performed, which revealed a homozygous c.1693T>C;p.(Tyr565His) variant in the SLC6A17 gene. The variant segregated in the extended family with the phenotype. This study broadens the genotypic spectrum of SLC6A17 variants.
Archives of Medicine and Health Sciences · 2023 · 0 citations · open access
A Case Report of Hebephrenic Schizophrenia in Intellectual Disability with Subependymal Heterotopia
AbstractSubependymal heterotopia (SH), also commonly known as periventricular nodular heterotopia, is believed to result from a faulty neuronal migration which is associated with seizure disorders and intellectual disability. Intellectual developmental delay (IDD) is a condition of arrested or incomplete development of mind with the impairment of intelligence. Although SH and IDD co-occur often, cases of schizophrenia in SH with IDD are less commonly reported. A thorough search of scientific databases with keywords of IDD, SH, and schizophrenia on PubMed, Scopus, and Google Scholar combined yielded limited results, prompting us to report this case of SH without any history of seizures who developed hebephrenic Schizophrenia. This highlights the need to check for the presence of SH by MRI scan in individuals with IDD and psychosis.
Journal of the Pakistan Medical Association · 2019 · 0 citations · open access
Fine mapping of MRT9 locus through genome wide homozygosity mapping in a consanguineous Pakistani family
AbstractIntellectual disability (ID) or Mental Retardation (MR) is a broad term, which occupies several medical directions. It is extremely heterogeneous and has about reported 25,000 genes of which half of the genes expression have been found in the brain. Intellectual disability causes severe disability and has a worldwide prevalence ofaround 2% while autosomal recessive form of ID causes almost 25% of all non syndromic (NS) ID cases. A consanguineous family (who will be referred as) MR7 with phenotype of ID was sampled in Swat region of Pakistan.All affected individuals in the family were observed having a low IQ and cognitive mutilation with no sign of biochemical, skeletal or neurological abnormalities. Continou....
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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