DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for sandestig-stefanova 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 moduleSandestig-stefanova 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 sandestig-stefanova 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.
What the evidence adds up to
Sandestig-Stefanova syndrome is an autosomal recessive disorder caused by bi-allelic loss-of-function variants in the NUP188 gene. Fewer than 15 cases have been described in the literature. A 2025 report identified a novel homozygous splice variant (NM_015354.2 c.1962-2A>C) in a Saudi patient. RT-PCR showed no detectable amplification in the proband, while parental samples displayed two bands consistent with carrier status. The patient had involvement of the ophthalmologic, central nervous, skin, cardiac, and respiratory systems, and died of respiratory failure. A 2024 report described a patient with a novel homozygous truncating variant (c.124C>T, p.Arg42Ter) who presented with tetralogy of Fallot, bilateral congenital cataracts, hydrocephalus, bifid uvula, right pelvic kidney, hepatomegaly, and characteristic facial features; a similarly affected sibling had died previously.
The core phenotype includes pre- and postnatal microcephaly, trigonocephaly, bilateral congenital cataracts, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, periventricular white matter loss, thin corpus callosum, and delayed myelination. Both new reports expand the known allelic spectrum and the range of clinical features, with hydrocephalus and tetralogy of Fallot now documented. No treatments or interventions were tested in any of these studies.
What remains missing is any preclinical model of the disease, any drug screening effort, and any trial design. There is no evidence for any drug that modifies the course of Sandestig-Stefanova syndrome. The fundamental gaps are the absence of a molecularly characterised cellular or animal model, the lack of a natural history study with quantitative outcome measures, and the absence of funding for any therapeutic development programme.
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 · 2025 · 1 citations
A Novel Homozygous Splice Variant in the <i>NUP188</i> Gene Causing Sandestig‐Stefanova Syndrome in a Saudi Patient
AbstractSandestig-Stefanova syndrome (SANDSTEF) (OMIM: 618804) is a recently identified autosomal recessive disorder characterized by a complex phenotype affecting multiple organ systems. To date, only 10 cases have been reported in the literature. Here, we present a newly identified patient exhibiting a distinct clinical presentation, along with a novel homozygous splice variant in NUP188. The proband has multiple system involvement, including ophthalmology, central nervous system, skin, distinct facial features, congenital heart disease, and respiratory system; eventually, he passed away with respiratory failure. A novel splice variant was identified using ES (NM_015354.2c.1962-2A>C p.(?)). The variant was confirmed by Sanger sequencing and was found to segregate from the parents. RT-PCR analysis showed no detectable amplification in the proband, while parental samples displayed two bands, indicating carrier status. The identification of a novel pathogenic variant contributes to a deeper understanding of the molecular mechanisms underlying the disorder and expands its phenotypic spectrum.
Molecular Syndromology · 2024 · 1 citations · open access
A Novel Truncating Variant in Sandestig-Stefanova Syndrome with Hydrocephalus
Abstract<b><i>Introduction:</i></b> Sandestig-Stefanova syndrome (MIM:618804) is characterized by pre- and postnatal microcephaly, trigonocephaly, bilateral congenital cataracts, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, periventricular white matter loss, thin corpus callosum, and delayed myelination. Bi-allelic loss-of-function variants in the <i>Nucleoporin 188 (NUP188)</i> (MIM:615587) gene are implicated in the etiology. <b><i>Case Presentation:</i></b> Our patient, born to consanguineous parents, presented with tetralogy of Fallot, bilateral congenital cataracts, hydrocephalus, a bifid uvula, a right pelvic kidney, hepatomegaly, facial feature findings, and a history of a similarly affected ex-sibling. Whole exome sequence analysis in the index case revealed a novel homozygous variant NM_015354.2: c.124C&gt;T/p.(Arg42Ter) in the <i>NUP188</i> gene. <b><i>Conclusion:</i></b> This study describes a new patient with Sandestig-Stefanova syndrome harboring a novel pathogenic variant in the <i>NUP188</i> gene.
Supplementary Material for: A novel truncating variant in Sandestig-Stefanova syndrome with Hydrocephalus
AbstractIntroduction: Sandestig-Stefanova Syndrome (MIM:#618804) is characterized by pre- and postnatal microcephaly, trigonocephaly, bilateral congenital cataracts, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, periventricular white matter loss, thin corpus callosum, and delayed myelination. Bi-allelic loss-of-function variants in the Nucleoporin 188 (NUP188) (MIM:#615587) gene are implicated in the etiology. Case presentation: Our patient, born to consanguineous parents, presented with tetralogy of Fallot, bilateral congenital cataracts, hydrocephalus, a bifid uvula, a right pelvic kidney, hepatomegaly, facial feature findings, and a history of a similarly affected ex-sibling. Whole exome sequence analysis in the index case revealed a novel homozygous variant NM_015354.2: c.124C>T (p.Arg42Ter) in the NUP188 gene. Conclusion: This study describes a new patient with Sandestig-Stefanova Syndrome harboring a novel pathogenic variant in the NUP188 gene.
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.
