ArticleAmerican journal of human genetics2009
Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed, 160 citations in OpenAlex.
- Temporal loss ofGenes & development · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
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- Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.Journal of human genetics · 2025Review
- Evolution and Comparative Genomics of the Transforming Growth Factor-β-Related Proteins in Nile Tilapia.Molecular biotechnology · 2025Article
- Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development.Nature ecology & evolution · 2025Article
- WNT signaling coordinately controls mouse limb bud outgrowth and establishment of the digit-interdigit pattern.Development (Cambridge, England) · 2025Article
- In Silico Analysis: Genome-Wide Identification, Characterization and Evolutionary Adaptations of Bone Morphogenetic Protein (BMP) Gene Family in Homo sapiens.Molecular biotechnology · 2024Article
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- ROR2-Related Skeletal Dysplasia Reveals Disrupted Chondrocyte Polarity through Modulation of BMP/TGF-β Signaling.Aging and disease · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- TGF-β signaling in health and disease.Cell · 2023Review
- Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.Nature genetics · 2023Article
- A novel variant in the ROR2 gene underlying brachydactyly type B: a case report.BMC pediatrics · 2022Article
- A 6.3 Mb maternally derived microduplication of 20p13p12.2 in a fetus with Brachydactyly type D and related literature review.Molecular cytogenetics · 2022Article
- Prospects of Non-Coding Elements in Genomic DNA Based Gene Therapy.Current gene therapy · 2022Review
- Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity.Nature communications · 2021Article
- GLIS Family Zinc Finger 1 was First Linked With Preaxial Polydactyly I in Humans by Stepwise Genetic Analysis.Frontiers in cell and developmental biology · 2021Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal-dominant brachydactyly type A2 (BDA2), a limb malformation characterized by hypoplastic middle phalanges of the second and fifth fingers, has been shown to be due to mutations in the Bone morphogenetic protein receptor 1B (BMPR1B) or in its ligand Growth and differentiation factor 5 (GDF5). A linkage analysis performed in a mutation-negative family identified a novel locus for BDA2 on chromosome 20p12.3 that incorporates the gene for Bone morphogenetic protein 2 (BMP2). No point mutation was identified in BMP2, so a high-density array CGH analysis covering the critical interval of approximately 1.3 Mb was performed. A microduplication of approximately 5.5 kb in a noncoding sequence approximately 110 kb downstream of BMP2 was detected. Screening of other patients by qPCR revealed a similar duplication in a second family. The duplicated region contains evolutionary highly conserved sequences suggestive of a long-range regulator. By using a transgenic mouse model we can show that this sequence is able to drive expression of a X-Gal reporter construct in the limbs. The almost complete overlap with endogenous Bmp2 expression indicates that a limb-specific enhancer of Bmp2 is located within the identified duplication. Our results reveal an additional functional mechanism for the pathogenesis of BDA2, which is duplication of a regulatory element that affects the expression of BMP2 in the developing limb.
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