DeCure for Chromosome 22q11.2 deletion syndrome, distal
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chromosome 22q11.2 deletion syndrome, distal — 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 moduleChromosome 22q11.2 deletion syndrome, distal 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 chromosome 22q11.2 deletion syndrome, distal 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
ATP binding cassette subfamily A member 3 (ABCA3) — ABCA3 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 px4drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7W01 · 3.3 Å · ligand 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PX4). Experimental structure, not a prediction.
What the evidence adds up to
Chromosome 22q11.2 deletion syndrome occurs in approximately 1 in 3000 children, or at least 1 in 5000 live births, making it the most common chromosomal deletion syndrome in humans. The deletion is usually up to 3 Mb on the long arm of chromosome 22, transmitted dominantly, though most cases are de novo mutations. The region contains low-copy repeats that make it unstable and susceptible to misalignment during nonallelic homologous recombination. Haploinsufficiency of genes at 22q11.2, particularly TBX1, affects early morphogenesis of the pharyngeal arches, heart, skeleton, and brain. More than 180 clinical features have been described, but none is pathognomonic or obligatory. In a selected sample of 30 patients with clinical suspicion and normal karyotype, fluorescent in situ hybridisation identified the microdeletion in 3 patients (10%), a prevalence within the published range of 4 to 21%. Those patients shared few clinical features, confirming the difficulty of clinical diagnosis.
The clinical phenotype ranges from immune deficiency with thymic aplasia, congenital heart abnormalities, velopharyngeal insufficiency with hypernasal speech, and slight dysmorphy with characteristic facies, to severe syndromal developmental abnormalities with mental retardation. In childhood and adolescence, attention deficit hyperactivity disorder affects up to 55% of patients. Obsessive–compulsive disorder is a less frequent comorbidity in adolescence. In adulthood, there is increased prevalence of schizophrenic and bipolar affective psychoses. An 11-year-old boy with 22q11 deletion presented with a previously unreported combination of psychiatric disorder, hypoparathyroidism, and precocious puberty. The syndrome is now recognised as an excellent model for probing mechanisms underlying psychiatric disease and cardiovascular development.
Since 1997, work on clinical and basic science aspects of the syndrome and the genes reduced to hemizygosity has provided information on best practice care and underlying biology. Once identified, patients can receive appropriate multidisciplinary care. Autoimmune diseases have been noted in the syndrome. The term 22q11DS is used as an umbrella term encompassing all 22q11.2 deletion-associated phenotypes. The phenotypic spectrum is very wide, and even affected members from the same family may present with different features.
What is still missing is a systematic understanding of which specific genetic modifiers or environmental factors account for the extreme phenotypic variability, and whether precocious puberty is a genuine clue for the deletion. No drug treatment for the syndrome itself is described in these abstracts. Large, prospective, stratified natural-history studies that track psychiatric, endocrine, and immune outcomes from childhood into late adulthood are lacking, as is funding for such longitudinal work.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2002 · 133 citations
Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes)
AbstractChromosome 22q11.2 deletion syndrome occurs in approximately 1 of 3000 children. Clinicians have defined the phenotypic features associated with the syndrome and the past 5 years have seen significant progress in determining the frequency of the deletion in specific populations. As a result, caregivers now have a better appreciation of which patients are at risk for having the deletion. Once identified, patients with the deletion can receive appropriate multidisciplinary care. We describe recent advances in understanding the genetic basis for the syndrome, the clinical manifestations of the syndrome, and new information on autoimmune diseases in this syndrome.
The Application of Clinical Genetics · 2015 · 86 citations · open access
22q11 deletion syndrome: current perspective
AbstractChromosome 22q11 is characterized by the presence of chromosome-specific low-copy repeats or segmental duplications. This region of the chromosome is very unstable and susceptible to mutations. The misalignment of low-copy repeats during nonallelic homologous recombination leads to the deletion of the 22q11.2 region, which results in 22q11 deletion syndrome (22q11DS). The 22q11.2 deletion is associated with a wide variety of phenotypes. The term 22q11DS is an umbrella term that is used to encompass all 22q11.2 deletion-associated phenotypes. The haploinsufficiency of genes located at 22q11.2 affects the early morphogenesis of the pharyngeal arches, heart, skeleton, and brain. TBX1 is the most important gene for 22q11DS. This syndrome can ultimately affect many organs or systems; therefore, it has a very wide phenotypic spectrum. An increasing amount of information is available related to the pathogenesis, clinical phenotypes, and management of this syndrome in recent years. This review summarizes the current clinical and genetic status related to 22q11DS.
The International Journal of Neuropsychopharmacology · 2006 · 15 citations · open access
22q11.2 deletion syndrome as a natural model for COMT haploinsufficiency-related dopaminergic dysfunction in ADHD
AbstractIn the current issue of IJNP Gothelf and co-workers report an important study which sheds light on the association between chromosome 22q11.2 deletion syndrome (22q11.2 DS; velocardiofacial syndrome, VCFS), dopaminergic transmission, and psychiatric disorders. 22q11.2 DS occurs in at least 1/5000 live births and thus is the most common chromosomal deletion syndrome in humans (Botto et al., 2003). The deletion in the long arm of chromosome 22, usually comprises up to 3 Mb, and is transmitted dominantly, although most patients suffer from de-novo mutations. The clinical phenotype ranges from immune deficiency with thymal aplasia, congenital heart abnormalities, velopharyngeal insufficiency with hypernasal speech, slight dysmorphy with characteristic facies, to severe syndromal developmental abnormalities with mental retardation (Shprintzen, 2000). Most interestingly for the field of neuropsychiatry, 22q11.2 DS is associated with an increased rate of variety of psychiatric disorders. In childhood and adolescence, 22q11.2 DS is associated with attention deficit hyperactivity disorder (ADHD; Antshel et al., 2005; Niklasson et al., 2002), affecting up to 55% of the patients (Gothelf et al., 2004). Another, less frequent comorbidity in adolescence seems to be obsessive–compulsive disorder (OCD; Gothelf et al., 2006). Finally, there is an increased prevalence for comorbidity with schizophrenic and bipolar affective psychoses in adulthood (Murphy, 2005).
Revista da Associação Médica Brasileira · 2009 · 10 citations · open access
Síndrome de deleção 22q11.2: importância da avaliação clínica e técnica de FISH
AbstractOBJECTIVE: The 22q11.2 deletion syndrome nowadays is considered one of the most often observed genetic diseases in humans. It is clinically characterized by a rather wide phenotypic spectrum, with more than 180 clinical features physical as well as behavioral, already described. However, none is pathognomonic or obligatory which makes diagnosis even more difficult. Thus, this study intended to determine the prevalence and clinical characteristics of patients with 22q11.2 microdeletion in a selected sample of subjects with clinical suspicion of 22q11.2 deletion syndrome and normal karyotype. METHODS: A selected sample of 30 patients with clinical suspicion of 22q11.2 deletion syndrome and normal karyotype was evaluated by application of a standard clinical protocol and cytogenetic analysis with fluorescent in situ hybridization. RESULTS: 22q11.2 microdeletion was identified in 3 patients (10%), a prevalence similar to the majority of published studies, which ranged from 4 to 21%. The 22q11.2 deletion syndrome patients in this study were characterized by a variable phenotype and shared few clinical features, in agreement with the literature description. CONCLUSIONS: These findings strengthen the idea that clinical diagnosis of 22q11.2 deletion syndrome is difficult due to the large phenotypic variability. Therefore a detailed clinical evaluation associated to a sensitive test such as fluorescent in situ hybridization analysis is crucial for the identification of these patients.
AbstractThe article analyzes the consequences of chromosomal abnormalities caused by the deletion of a small piece of chromosome 22. This syndrome results in diverse clinical manifestations: congenital heart defects, abnormalities in the large vessels, congenital defects in the maxillofacial area, as well as the endocrine and immune disorders. 22q11.2 deletion syndrome — del 22q11.2 (22q11DS) may have more than 180 different physical, functional and mental associations that affect the patient’s health and quality of life since very birth. Clinical diagnosis and early diagnostics are essential to optimize treatment, and awareness and understanding of the pathological processes in del 22q11.2 definitely involve the use of the multidisciplinary treatment principles. The article describes the modern scientific understanding of 22q11.2 deletion syndrome based on the experience of foreign and Russian authors. The basic clinical symptoms, diagnosis and recommendations for screening and treatment of this kind of patients are described.
Journal of Pediatric Endocrinology and Metabolism · 2006 · 1 citations
An Unusual Case of Chromosome 22q11 Deletion Syndrome with Psychiatric Disorder, Hypoparathyroidism and Precocious Puberty
AbstractDeletions of chromosome 22q11 cause a wide range of phenotypes; even affected members from the same family may present with different phenotype. We present an 11-3/12 year-old boy who has 22q11 deletion in a hitherto unreported combination with psychiatric disorder, hypoparathyroidism and precocious puberty. Whether precocious puberty is a clue for chromosome 22q11 deletion syndrome is also discussed.
Journal of Medical Genetics · 2025 · 0 citations · open access
Six at Sixty. ‘Have you tested for 22q?’
Abstractpublished our paper on the spectrum of clinical features associated with interstitial chromosome 22q11 deletions. This copy number variation is associated with an extraordinary range of clinical features, which led initially to its association with several diagnostic labels. Since 1997 work on clinical and basic science aspects of the syndrome and the genes reduced to hemizygosity have provided a wealth of information pertaining to both best practice care and underlying biology. It is recognised that 22q11.2 deletion syndrome is an excellent model for probing mechanisms underlying psychiatric disease, cardiovascular development and much more.
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.
