ArticleProceedings of the National Academy of Sciences of the United States of America2003
Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- The molecular genetics of human appendicular skeleton.Molecular genetics and genomics : MGG · 2022Pooled it
- Metabolic rewiring during bone development underlies tRNA m7G-associated primordial dwarfism.The Journal of clinical investigation · 2024Article
- Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction.BMC medical genomics · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- A Genetic Approach in the Evaluation of Short Stature.The Eurasian journal of medicine · 2022Article
- Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Article
- Signaling network regulating osteogenesis in mesenchymal stem cells.Journal of cell communication and signaling · 2022Review
- A 6.3 Mb maternally derived microduplication of 20p13p12.2 in a fetus with Brachydactyly type D and related literature review.Molecular cytogenetics · 2022Article
- Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization.Nature communications · 2021Article
- Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling.Nature communications · 2021Article
- BMPR1B gene in brachydactyly type 2-A family with de novo R486W mutation and a disease phenotype.Molecular genetics & genomic medicine · 2021Article
- Whole-exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis.Molecular genetics & genomic medicine · 2020Article
- Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate.World journal of experimental medicine · 2020Article
- Endoplasmic Reticulum Associated Protein Degradation (ERAD) in the Pathology of Diseases Related to TGFβ Signaling Pathway: Future Therapeutic Perspectives.Frontiers in molecular biosciences · 2020Review
- Bone morphogenetic protein receptor signal transduction in human disease.The Journal of pathology · 2019Review
- Article
- Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility.European journal of human genetics : EJHG · 2018Article
- Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12 Deletions.American journal of human genetics · 2017Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brachydactyly (BD) type A2 is an autosomal dominant hand malformation characterized by shortening and lateral deviation of the index fingers and, to a variable degree, shortening and deviation of the first and second toes. We performed linkage analysis in two unrelated German families and mapped a locus for BD type A2 to 4q21-q25. This interval includes the gene bone morphogenetic protein receptor 1B (BMPR1B), a type I transmembrane serinethreonine kinase. In one family, we identified a T599 --> A mutation changing an isoleucine into a lysine residue (I200K) within the glycine/serine (GS) domain of BMPR1B, a region involved in phosphorylation of the receptor. In the other family we identified a C1456 --> T mutation leading to an arginine-to-tryptophan amino acid change (R486W) in a highly conserved region C-terminal of the BMPR1B kinase domain. An in vitro kinase assay showed that the I200K mutation is kinase-deficient, whereas the R486W mutation has normal kinase activity, indicating a different pathogenic mechanism. Functional analyses with a micromass culture system revealed a strong inhibition of chondrogenesis by both mutant receptors. Overexpression of mutant chBmpR1b in vivo in chick embryos by using a retroviral system resulted either in a BD phenotype with shortening and/or missing phalanges similar to the human phenotype or in severe hypoplasia of the entire limb. These findings imply that both mutations identified in human BMPR1B affect cartilage formation in a dominant-negative manner.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.