ArticleAmerican journal of human genetics2015
Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- The pathogenesis and intersecting mechanisms of monogenic bone mass disorders.Nature reviews. Endocrinology · 2026Review
- When truncation is not loss of function: neo-tail architecture as a determinant of pathogenicity in NMD-escaping frameshift variants.European journal of human genetics : EJHG · 2026Article
- Robinow syndrome DVL1 variants disrupt morphogenesis and appendage formation in a Drosophila disease model.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Clarifying Frizzled 2 function in development through genetically validated mouse models.Disease models & mechanisms · 2026Article
- Identification and functional characterization of a novel pathogenic DVL1 gene variant in Robinow syndrome.Molecular genetics and genomics : MGG · 2026Article
- The abnormal C-terminus caused by DVL1 variants impacts Robinow syndrome phenotypes.Human molecular genetics · 2026Article
- Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling.Biochemistry and biophysics reports · 2026Article
- Genetic Regulation of Wnt/PCP Components Through Fgf10/Fgfr2/Sox9 Module in Tear Duct Development.Investigative ophthalmology & visual science · 2026Article
- Genetic Variants in DVL3 are Associated With Root Maldevelopment, Tooth Agenesis, Mesiodens, and Oral Exostoses.International dental journal · 2026Article
- Comprehensive Clinical, Diagnostic, and In Silico Assessment of a Novel 1p36.33p36.32 Copy Number Variant.Journal of cellular and molecular medicine · 2026Article
- Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor.Nature communications · 2025Article
- ATranslational pediatrics · 2025Article
- Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.eLife · 2024Article
- Core planar cell polarity genesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia.American journal of human genetics · 2023Article
- Mechanistic studies in Drosophila and chicken give new insights into functions of DVL1 in dominant Robinow syndrome.Disease models & mechanisms · 2023Article
- Article
- Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway.Current topics in developmental biology · 2023Article
- TBX6 as a cause of a combined skeletal-kidney dysplasia syndrome.American journal of medical genetics. Part A · 2022Article
- Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.Human mutation · 2022Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Robinow syndrome (RS) is a phenotypically and genetically heterogeneous condition that can be caused by mutations in genes encoding components of the non-canonical Wnt signaling pathway. In contrast, germline mutations that act to increase canonical Wnt signaling lead to distinctive osteosclerotic phenotypes. Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals. The mutations all delete the DVL1 C terminus and replace it, in each instance, with a novel, highly basic sequence. We showed the presence of mutant transcript in fibroblasts from one individual with RS-OS and demonstrated unimpaired protein stability with transfected GFP-tagged constructs bearing a frameshift mutation. In vitro TOPFlash assays, in apparent contradiction to the osteosclerotic phenotype, revealed that the mutant allele was less active than the wild-type allele in the canonical Wnt signaling pathway. However, when the mutant and wild-type alleles were co-expressed, canonical Wnt activity was 2-fold higher than that in the wild-type construct alone. This work establishes that DVL1 mutations cause a specific RS subtype, RS-OS, and that the osteosclerosis associated with this subtype might be the result of an interaction between the wild-type and mutant alleles and thus lead to elevated canonical Wnt signaling.
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