DeCure for Congenital dyserythropoietic anemia type 4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital dyserythropoietic anemia type 4 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital dyserythropoietic anemia type 4 maps to a 2-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 congenital dyserythropoietic anemia type 4 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
glutaryl-CoA dehydrogenase (GCDH) — GCDH 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2R0N · 2.3 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
In a 2009 study of 42 patients with congenital dyserythropoietic anaemia type II, sequencing of the SEC23B gene found 22 mutations, including seven novel ones. Patients with one missense and one nonsense mutation tended to have more severe clinical presentation, lower reticulocyte count, higher serum ferritin, and in some cases more pronounced transfusion needs than patients with two missense mutations. No patient was homozygous or compound heterozygous for two nonsense mutations. The authors noted overlap between the two categories.
A 2001 case report describes a patient with congenital dyserythropoietic anaemia type I who had intrauterine onset of severe anaemia leading to cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration despite the severity of anaemia. After repeated transfusions and a trial of erythropoietin, the patient died from respiratory infection at age 7 months. Autopsy confirmed the diagnosis by light and electron microscopy.
A 2018 study using targeted gene panel sequencing in 53 patients from 44 unrelated families found pathogenic variants in 21 patients. Six variants were in CDAN1, twelve in SEC23B, one in KLF1, and one in ALAS2. Some SEC23B-monoallelic patients had genomic rearrangements detected by comparative genome hybridisation. The authors noted that new technologies would help find variants in other genes that contribute to or modulate the CDA phenotype.
A 2020 case report describes the ninth reported patient with congenital dyserythropoietic anaemia type IV, carrying a novel mutation in the KLF1 gene that had not been reported before. A 1985 report describes a family with mild anaemia, marked dyserythropoiesis, prominent ringed sideroblasts, microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, and bone marrow erythroid hyperplasia, proposing the designation variant congenital dyserythropoietic anaemia with ringed sideroblasts. What is still missing for all these forms is systematic prospective natural history data, standardised outcome measures, and any controlled trial of a therapeutic agent. No drug has been tested in a randomised fashion for any CDA subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2009 · 62 citations · open access
Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship
AbstractBACKGROUND: The most frequent form of congenital dyserythropoietic anemia is the type II form. Recently it was shown that the vast majority of patients with congenital dyserythropoietic anemia type II carry mutations in the SEC23B gene. Here we established the molecular basis of 42 cases of congenital dyserythropoietic anemia type II and attempted to define a genotype-phenotype relationship. DESIGN AND METHODS: SEC23B gene sequencing analysis was performed to assess the diversity and incidence of each mutation in 42 patients with congenital dyserythropoietic anemia type II (25 described exclusively in this work), from the Italian and the French Registries, and the relationship of these mutations with the clinical presentation. To this purpose, we divided the patients into two groups: (i) patients with two missense mutations and (ii) patients with one nonsense and one missense mutation. RESULTS: We found 22 mutations of uneven frequency, including seven novel mutations. Compound heterozygosity for a missense and a nonsense mutation tended to produce a more severe clinical presentation, a lower reticulocyte count, a higher serum ferritin level, and, in some cases, more pronounced transfusion needs, than homozygosity or compound heterozygosity for two missense mutations. Homozygosity or compound heterozygosity for two nonsense mutations was never found. CONCLUSIONS: This study allowed us to determine the most frequent mutations in patients with congenital dyserythropoietic anemia type II. Correlations between the mutations and various biological parameters suggested that the association of one missense mutation and one nonsense mutation was significantly more deleterious that the association of two missense mutations. However, there was an overlap between the two categories.
Congenital Dyserythropoietic Anemia Type 1 With Fetal Onset of Severe Anemia
AbstractWe report a patient with congenital dyserythropoietic anemia type 1 with characteristic anomalies and two novel clinicopathologic presentations: intrauterine onset of severe anemia resulting in cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration in contrast to severity of anemia. After repeated transfusions and a trial of erythropoietin administration, the patient died from respiratory infection at age 7 months. Autopsy revealed characteristic dyserythropoietic features of the bone marrow by light microscopy and electron microscopy, which confirmed a diagnosis of congenital dyserythropoietic anemia type 1.
European Journal Of Haematology · 2018 · 17 citations
Clinical and genetic features of congenital dyserythropoietic anemia (<scp>CDA</scp>)
AbstractINTRODUCTION: Congenital dyserythropoietic anemias (CDA) are characterized by hyporegenerative anemia with inadequate reticulocyte values, ineffective erythropoiesis, and hemolysis. Distinctive morphology of bone marrow erythroblasts and identification of causative genes allow classification into 4 types caused by variants in CDAN1, c15orf41, SEC23B, KIF23, and KLF1 genes. OBJECTIVE: Identify pathogenic variants in CDA patients. METHODS: Massive parallel sequencing with a targeted gene panel, Sanger sequencing, Comparative Genome Hybridization (CGH), and in silico predictive analysis of pathogenicity. RESULTS: Pathogenic variants were found in 21 of 53 patients studied from 44 unrelated families. Six variants were found in CDAN1: two reported, p.Arg714Trp and p.Arg725Trp and, four novel, p.Arg623Trp, p.Arg946Trp, p.Phe1125Ser and p.Ser1227Gly. Twelve variants were found in SEC23B: seven reported, p.Arg14Trp, p.Glu109Lys, p.Arg217Ter, c.835-2A>G, p.Arg535Ter, p.Arg550Ter and p.Arg718Ter and, five novel, p.Val164Leu, p.Arg190Gln, p.Gln521Ter, p.Arg546Trp, and p.Arg611Gln. The variant p.Glu325Lys in KLF1 was found in one patient and p.Tyr365Cys in ALAS2 in an other. Moreover, we identified genomic rearrangements by CGH in some SEC23B-monoallelic patients. CONCLUSIONS: New technologies for genetic studies will help to find variants in other genes, in addition to those known, that contribute to or modulate the CDA phenotype or support the correct diagnosis.
Journal of Pediatric Hematology/Oncology · 2020 · 15 citations
A Very Rare Congenital Dyserythropoietic Anemia Variant—Type IV in a Patient With a Novel Mutation in the KLF1 Gene: A Case Report and Review of the Literature
AbstractCongenital dyserythropoietic anemias comprise a group of very rare hereditary disorders characterized by ineffective erythropoiesis and distinct morphologic abnormalities of the erythroblasts in the bone marrow. The wide variety of phenotypes observed in these patients makes the diagnosis difficult; identification of the genetic variants is crucial in differential diagnosis and clinical management. We report the nineth case with congenital dyserythropoietic anemia type IV, with a novel mutation that has not been reported before.
Variant congenital dyserythropoietic anaemia with ringed sideroblasts
AbstractA family is described with mild anaemia characterized by marked dyserythropoiesis and by prominent ringed sideroblasts. Inheritance is autosomal recessive. Other features include marked microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, bone marrow erythroid hyperplasia and non-specific structural abnormalities of erythroid precursors on electron microscopy. This appears to be a previously unreported type of hereditary anaemia with both dyserythropoiesis and ringed sideroblasts. We propose the designation 'variant congenital dyserythropoietic anaemia with ringed sideroblasts'.
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.
