ArticleHuman molecular genetics2018
Functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome phenotype.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 30 citations in OpenAlex.
- Interactions between small leucine-rich proteoglycans and proteases: implications for tissue homeostasis and pathology.The FEBS journal · 2026Review
- From pixels to pimples.JID innovations : skin science from molecules to population health · 2026Article
- The Genetics of Acne.Annals of human genetics · 2025Review
- Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration.Nature communications · 2025Article
- Zebrafish as a Model for Osteoporosis: Functional Validations of Genome-Wide Association Studies.Current osteoporosis reports · 2023Review
- An injury-responsiveScience advances · 2023Article
- Loss of CSF-contacting neuron sensory function is associated with a hyper-kyphosis of the spine reminiscent of Scheuermann's disease.Scientific reports · 2023Article
- A novel gene mutation for multicentric osteolysis nodulosis and arthropathy: Case report and review of literature.Heliyon · 2023Article
- Gene expression patterns associated with caudal fin shape in the cichlidHydrobiologia · 2023Article
- Review
- Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations.Bone reports · 2021Article
- Metalloproteases in gonad formation and ovulation.General and comparative endocrinology · 2021Review
- Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2021Review
- Genetic association of MMP14 promoter variants and their functional significance in gallbladder cancer pathogenesis.Journal of human genetics · 2021Article
- Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review).Molecular medicine reports · 2021Review
- Zebrafish Models for Human Skeletal Disorders.Frontiers in genetics · 2021Review
- The novel zebrafish modelBiology open · 2020Article
- Genetic regulation of linear growth.Annals of pediatric endocrinology & metabolism · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 11 institutions in 5 countries.
Funding
Abstract
Winchester syndrome (WS, MIM #277950) is an extremely rare autosomal recessive skeletal dysplasia characterized by progressive joint destruction and osteolysis. To date, only one missense mutation in MMP14, encoding the membrane-bound matrix metalloprotease 14, has been reported in WS patients. Here, we report a novel hypomorphic MMP14 p.Arg111His (R111H) allele, associated with a mitigated form of WS. Functional analysis demonstrated that this mutation, in contrast to previously reported human and murine MMP14 mutations, does not affect MMP14's transport to the cell membrane. Instead, it partially impairs MMP14's proteolytic activity. This residual activity likely accounts for the mitigated phenotype observed in our patients. Based on our observations as well as previously published data, we hypothesize that MMP14's catalytic activity is the prime determinant of disease severity. Given the limitations of our in vitro assays in addressing the consequences of MMP14 dysfunction, we generated a novel mmp14a/b knockout zebrafish model. The fish accurately reflected key aspects of the WS phenotype including craniofacial malformations, kyphosis, short-stature and reduced bone density owing to defective collagen remodeling. Notably, the zebrafish model will be a valuable tool for developing novel therapeutic approaches to a devastating bone disorder.
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.