DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Jalili 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 moduleJalili 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 jalili 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
cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) — CNNM4 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9Y9D · 3.48 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Jalili syndrome is a rare autosomal recessive disorder defined by the combination of cone-rod dystrophy and amelogenesis imperfecta. A 2011 case report of a 9-year-old child with both neurofibromatosis type 1 and Jalili syndrome confirmed the diagnosis of Jalili syndrome through clinical examination and molecular genetic analysis of the CNNM4 gene, which had previously been shown to cause the condition. The authors described this as a unique but random association of two diseases. A 2023 report described the first genetically confirmed paediatric case from the Indian subcontinent, in a 6-year-old child, and noted that high fluoride concentration in groundwater has been identified as an epigenetic factor in the syndrome.
The cone-rod dystrophy in Jalili syndrome involves progressive loss of visual acuity, colour blindness, and photophobia. The amelogenesis imperfecta can be hypoplastic, immature, or hypocalcified. A 2017 report of three brothers with Jalili syndrome and muscle overgrowth of the legs found a novel homozygous missense substitution in CNNM4 (c.1076T>C, p.(Leu359Pro)). Needle electromyography showed myopathic changes, and exome sequencing and MLPA analysis of the DMD gene in one patient did not identify any additional variants. The authors suggested that mild myopathy with muscle overgrowth of the legs could be a newly identified manifestation of the disorder.
A 2019 systematic review summarised reported clinical symptoms, CNNM4 gene and protein structure, CNNM4 mutations, attempts to reach a genotype-phenotype correlation, and the functional role of CNNM4 mutations. The review noted that Jalili syndrome has been observed in many countries, especially in the Middle East and North Africa. No drug treatment for the underlying condition is mentioned in any of these abstracts.
What is still missing is any clinical trial of a therapy, any funded effort to develop one, and any understanding of how the CNNM4 mutation leads to the tissue-specific damage in retina and enamel, or why some patients develop muscle overgrowth. Patient stratification beyond the known genetic diagnosis does not exist.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ophthalmic Genetics · 2011 · 18 citations
Cone-rod dystrophy associated with amelogenesis imperfecta in a child with neurofibromatosis type 1
AbstractPURPOSE: To report a case of a 9-year-old child with neurofibromatosis type 1 (NF1) and Jalili syndrome, the latter denoting a rare combination of cone-rod dystrophy and amelogenesis imperfecta. METHODS: Detailed ophthalmological and electrophysiological examinations were carried out and blood samples were taken from the patient and her father for molecular genetic analysis by direct DNA sequencing of the NF1 and the ancient conserved domain protein 4 (CNNM4) gene. RESULTS: The diagnosis of neurofibromatosis type 1 (NF1) could be confirmed clinically and genetically. Furthermore, cone-rod dystrophy and amelogenesis imperfecta could be observed as typical features of a rare condition, acknowledged as Jalili syndrome. The diagnosis was assured on the basis of clinical examinations and molecular genetic analysis of the CNNM4 gene, which was previously shown to cause Jalili syndrome. CONCLUSION: Our case shows a unique combination of NF1 and Jalili syndrome. The random association of two diseases is unusual and deserves attention. This case highlights the importance not only of detailed clinical examination, but also of molecular genetic analysis, which together provide a precise diagnosis.
Features, genetics and their correlation in Jalili syndrome: a systematic review
AbstractJalili syndrome is a rare genetic disorder first identified by Jalili in Gaza. Amelogenesis imperfecta and cone-rode dystrophy are simultaneously seen in Jalili syndrome patients as the main and primary manifestations. Molecular analysis has revealed that the CNNM4 gene is responsible for this rare syndrome. Jalili syndrome has been observed in many countries around the world, especially in the Middle East and North Africa. In the current scoping systematic review we searched electronic databases to find studies related to Jalili syndrome. In this review we summarise the reported clinical symptoms, CNNM4 gene and protein structure, CNNM4 mutations, attempts to reach a genotype-phenotype correlation, the functional role of CNNM4 mutations, and epidemiological aspects of Jalili syndrome. In addition, we have analysed the reported mutations in mutation effect prediction databases in order to gain a better understanding of the mutation’s outcomes.
American Journal of Medical Genetics Part A · 2017 · 10 citations
Co‐occurrence of Jalili syndrome and muscular overgrowth
AbstractJalili syndrome is a rare disorder inherited in an autosomal recessive pattern manifesting as a combination of cone-rod dystrophy including progressive loss of visual acuity, color blindness, photophobia, and amelogenesis imperfecta with hypoplastic, immature, or hypocalcified dental enamel. It is caused by mutations in CNNM4, which encodes the ancient conserved domain protein 4. Here we report three brothers with Jalili syndrome and muscle overgrowth of the legs. Myopathic changes were found in needle electromyography. Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant. In order to exclude other causative variants that could modify the patients' phenotype we performed exome sequencing and MLPA analysis of the DMD gene in Patient 1. These analyses did not identify any additional variants. Our results expand the mutational spectrum associated with Jalili syndrome and suggest that mild myopathy with muscle overgrowth of the legs could be a newly identified manifestation of the disorder.
Dentofacial manifestations in a child with Jalili syndrome
AbstractJalili syndrome (JS) (MIM#217080) is a rare autosomal recessive disorder with oculo-dental malformations. The clinical phenotype is characterized by the presence of Cone-Rod Dystrophy (CRD) and Amelogenesis Imperfecta (AI). Genetic mechanism entails a mutation in the CNNM4, a metal transporter gene located on Chromosome 2q11.2. A high fluoride concentration in groundwater has also been identified as an epigenetic factor in this syndrome. JS draws the attention of dentists due to its distinct oral manifestations. To the best of our knowledge, this is the first genetically confirmed pediatric case report from the Indian subcontinent emphasizing the clinical and radiographic features of this condition and its management in a 6-year-old child.
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.
