Rare & Orphan Lab · DeCure for X
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for acromesomelic dysplasia — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
No approved-drug candidate for acromesomelic dysplasia 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.
protein kinase cGMP-dependent 2 (PRKG2) — PRKG2 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.
RCSB Protein Data Bank · entry 5JIX · 1.47 Å · ligand 3,6,9,12,15,18,21,24-OCTAOXAHEXACOSAN-1-OL (PE5). Experimental structure, not a prediction.
Acromesomelic dysplasia is a group of inherited skeletal disorders causing extremely short stature, with autosomal recessive transmission. A 1980 summary states that radiographic features allow diagnosis in affected individuals over six months of age, and that establishing the diagnosis has practical importance due to the condition’s genetic pattern and resulting short stature.
A 2018 study of a consanguineous Pakistani family segregating the Hunter–Thompson subtype identified a novel homozygous missense variant in BMPR1B (c.1190T > G, p.Met397Arg). Linkage analysis produced a logarithm of odds score of 3.9 with the disease phenotype. This is the first reported familial case of acromesomelic dysplasia Hunter–Thompson type and the first report of BMPR1B underlying that subtype. The abstract notes that acromesomelic dysplasia is genetically heterogeneous and is caused by biallelic variants in three known genes: NPR2, GDF5, and BMPR1B.
A 2000 study used homozygosity mapping in four affected individuals and 11 first-degree relatives from four related nuclear families on St Helena island. Six consecutive markers on chromosome 9, spanning about 5 cM, showed identical homozygosity in all affected individuals, and multipoint analysis generated a maximum lod score of 2.85. The gene for this form was localised to the pericentromeric region of chromosome 9, where the Maroteaux form of acromesomelic dysplasia is also situated. No treatment or intervention is mentioned in any of these abstracts. What remains missing is any trial design, any patient stratification beyond genetic subtype, and any funding for therapeutic development — the reports are purely genetic and diagnostic.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThe radiographic features of acromesomelic dysplasia are presented, along with a summary of pertinent clinical features. They are thought to allow a diagnosis in affected individuals over six months of age. Since the condition has an autosomal recessive mode of genetic transmission and results in extremely short stature, the establishment of the diagnosis has practical importance.
https://doi.org/10.1148/radiology.137.2.7433666AbstractAcromesomelic dysplasia is genetically heterogeneous group of skeletal disorders characterized by short stature and acromelia and mesomelia of limbs. Acromesomelic dysplasia segregates in an autosomal recessive pattern and is caused by biallelic sequence variants in three genes (NPR2, GDF5, and BMPR1B). A consanguineous family of Pakistani origin segregating a subtype of acromesomelic dysplasia called Hunter-Thompson was clinically and genetically evaluated. Genotyping of microsatellite markers and linkage analysis revealed a 7.78 Mb homozygous region on chromosome 4q22.3, which harbors BMPR1B. Sequence analysis of the gene revealed a novel homozygous missense variant (c.1190T > G, p.Met397Arg) that segregates with the disease phenotype within the family and produced a Logarithm of odds (LOD) score of 3.9 with the disease phenotype. This study reports on the first familial case of acromesomelic dysplasia Hunter-Thompson type. It is also the first report of BMPR1B underlying the etiology of acromesomelic dysplasia Hunter-Thompson type.
https://doi.org/10.1111/ahg.12233AbstractThe acromesomelic dysplasias (AMDs) are a group of genetic disorders that primarily affect the middle and distal segments of the extremities. A form of AMD is present on the isolated island of St Helena in the South Atlantic, which has a population of approximately 5500 derived from a number of founder individuals. DNA from four affected individuals and 11 first-degree relatives in four related nuclear families segregating an AMD was collected for gene mapping studies. Six consecutive markers on chromosome 9, spanning an approximately 5 cM region, showed identical homozygosity in all affected individuals, thus identifying a region of homozygosity by descent. Multipoint analysis generated a maximum lod score of Z = 2.85. These data localize the gene for this dysplasia to the pericentromeric region of chromosome 9 where the gene for the Maroteaux form of AMD is situated. The identification of the gene responsible for this disorder may shed further light on the complex processes involved in limb morphogenesis.
https://doi.org/10.1034/j.1399-0004.2000.570406.xDisease 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.
