DeCure for Autosomal dominant deafness - onychodystrophy syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant deafness - onychodystrophy 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 moduleAutosomal dominant deafness - onychodystrophy 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 autosomal dominant deafness - onychodystrophy 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
ATPase H+ transporting V1 subunit B2 (ATP6V1B2) — ATP6V1B2 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WLZ · 2.9 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
In two unrelated families with dominant deafness-onychodystrophy (DDOD), whole-exome sequencing of 542 individuals from 166 families with congenital hearing loss identified the same nonsense mutation in ATP6V1B2 (c.1516C>T, p.R506*) in five affected individuals. This mutation was found in a mother and son from family 1 and in a father and daughter from family 2. The report states this is the first demonstration that ATP6V1B2-caused DDOD is an autosomal dominant genetic disease, as opposed to previous cases attributed to de novo mutation. In family 1, a novel heterozygous variant in TJP2 (c.1590T>G, p.D530E) was also detected in the patients. In family 2, a novel heterozygous variant in KIF11 (c.733A>G, p.M245V) was identified in a spouse with sensorineural hearing loss and epilepsy. Genotype-phenotype analysis of KIF11-associated disorders showed that p.M245V and two reported hearing-loss-associated variants map to a single β-sheet in the kinesin motor domain.
An earlier study from 1979 reported autosomal dominant atresia or stenosis of the external auditory canal with or without conductive deafness in 12 individuals across five generations of one family. Penetrance was very high, expressivity variable. Clinical, audiometric, radiographic, and operative findings were presented for three patients (grandfather, father, and son). The authors noted the condition had been reported only once previously.
A 2004 study of 743 children with hearing impairment under age 14 found earpits syndrome in 2 cases (0.27%). Both children were products of consanguineous marriage. One had mixed hearing loss, the other conductive hearing loss. No renal anomalies were detected in either case.
No drug treatment or intervention is mentioned in any of these abstracts. What remains missing is any clinical trial, any therapeutic candidate, any attempt to correct the underlying genetic variants, and any systematic natural history data that could inform trial design or patient stratification for this rare syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Genetics · 2021 · 9 citations · open access
Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
AbstractA cohort of 542 individuals in 166 families with congenital hearing loss was recruited for whole-exome sequencing analysis. Here, we report the identification of three variants in five affected individuals in two unrelated families. In family 1, a nonsense mutation (c.1516C>T, p.R506*) in the ATP6V1B2 gene, a known causal allele for dominant deafness-onychodystrophy (DDOD), was identified in the mother and son with DDOD. However, a novel heterozygous variant (c.1590T>G, p.D530E) in TJP2 , a known causal gene for hearing-loss, was also detected in the patients. In family 2, the same mutation (c.1516C>T, p.R506*) of ATP6V1B2 was detected from the father and daughter with DDOD. Furthermore, a novel heterozygous variant (c.733A>G, p.M245V) in the KIF11 gene was identified from the spouse with sensorineural hearing-loss and epilepsy. Notably, genotype-phenotype analysis of KIF11 -associated disorders revealed that the p.M245V and two reported hearing-loss-associated variants (p.S235C and p.H244Y) are all mapped to a single β-sheet (Ser235∼M245) in the kinesin motor domain. Together, this is the first demonstration that ATP6V1B2 -caused DDOD is an autosomal dominant genetic disease, compared to previous cases with de novo mutation. Our findings expand the variant spectrum of hearing-loss-associated genes and provide new insights on understanding of hearing-loss candidate genes ATP6V1B2 , TJP2 , and KIF11 .
American Journal of Medical Genetics · 1979 · 6 citations
Autosomal dominant atresia of the auditory canal and conductive deafness
AbstractWe report autosomal dominant atresia and/or stenosis of the external auditory canal with or without conductive deafness. In the family described here the anomaly had occurred in 12 individuals in five generations. Penetrance was very high, expressivity quite variable. The clinical, audiometric, radiographic, and operative findings in three patients (grandfather, father, and son) are presented. This condition has been reported only once previously.
International Journal of Human Genetics · 2004 · 0 citations
Earpits Syndrome in Children with Hearing Loss
AbstractEarpits syndrome is a very rare kind of syndrome deafness and inherited as autosomal dominant. A study was taken up to understand the prevalence of this syndrome in children below the age of 14 years with hearing loss. Out of 743 children with hearing impairment, earpits syndrome was observed in 2(0.27%) cases. Both the children were the products of consanguineous marriage. Mixed hearing loss was noticed in one case and conductive hearing loss in another case. However, no renal anomalies were detected in either of these cases.
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.
