ArticlePLoS genetics2013
A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.Journal of orthopaedic surgery and research · 2023Pooled it
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- A Novel HeterozygousPhenomics (Cham, Switzerland) · 2025Article
- A missenseJOR spine · 2024Article
- Sox, Fox, and Lmx1b binding sites differentially regulate a Gdf5-Associated regulatory region during elbow development.Frontiers in cell and developmental biology · 2023Article
- TATTOO-seq delineates spatial and cell type-specific regulatory programs in the developing limb.Science advances · 2022Article
- Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis.Nature communications · 2022Article
- Deep exploration of aJournal of medical genetics · 2022Article
- The third patient with Tsukahara-Azuno-Kaiji syndrome with type A1 brachydactyly, dwarfism, microcephaly, scoliosis, intellectual disability, ptosis, and hearing loss.Radiology case reports · 2022Article
- BMP signaling and skeletal development in fibrodysplasia ossificans progressiva (FOP).Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Interstitial duplication of 20q11.22q13.11: A case report and review of literature.Molecular genetics & genomic medicine · 2021Review
- Expression analysis of limb element markers during mouse embryonic development.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
- TGF-β Family Signaling in Early Vertebrate Development.Cold Spring Harbor perspectives in biology · 2018Review
- TGF-β Family Signaling in Mesenchymal Differentiation.Cold Spring Harbor perspectives in biology · 2018Review
- Knock-in human GDF5 proregion L373R mutation as a mouse model for proximal symphalangism.Oncotarget · 2017Article
- TGF-β Family Signaling in Connective Tissue and Skeletal Diseases.Cold Spring Harbor perspectives in biology · 2017Review
- The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Growth Differentiation Factor 5-Mediated Enhancement of Chondrocyte Phenotype Is Inhibited by Heparin: Implications for the Use of Heparin in the Clinic and in Tissue Engineering Applications.Tissue engineering. Part A · 2017Article
- A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5(W414R) variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain- and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA.
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.