ArticleThe Journal of clinical endocrinology and metabolism2023
Genotypic and Phenotypic Spectrum and Pathogenesis of WNT1 Variants in a Large Cohort of Patients With OI/Osteoporosis.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies.World journal of pediatrics : WJP · 2026Review
- Video-based gait analysis for clinical monitoring of genotype-specific functional patterns in osteogenesis imperfecta.BMC musculoskeletal disorders · 2026Article
- Non-COL1A1/2 genetic burden and osteoporosis-overlap in patients referred with osteogenesis imperfecta phenotype.Archives of osteoporosis · 2026Article
- Pediatric Scoliosis in Osteogenesis Imperfecta: From Genetic Mechanisms to Therapeutic Strategies.Orthopaedic surgery · 2025Review
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 2025Review
- Use of Teriparatide, Denosumab, and Romosozumab in a Postpartum Monogenic Osteoporosis With aJCEM case reports · 2025Article
- The gut microbiota in osteoporosis: dual roles and therapeutic prospects.Frontiers in immunology · 2025Review
- Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta.Journal of endocrinological investigation · 2024Article
- The role and mechanism of β-catenin-mediated skeletal muscle satellite cells in osteoporotic fractures by Jian-Pi-Bu-Shen formula.Journal of molecular histology · 2024Article
- Multi-omics analyses reveal aberrant differentiation trajectory with WNT1 loss-of-function in type XV osteogenesis imperfecta.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone research · 2024Review
- Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants.The Journal of clinical endocrinology and metabolism · 2024Article
- Article
- The hidden cross talk between bone and tissues through bone turnover.Advances in laboratory medicine · 2024Article
- Bone fragility and osteoporosis in children and young adults.Journal of endocrinological investigation · 2024Review
- Exploring the Role of Wnt Ligands in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.Clinical oral investigations · 2023Article
- Molecular and Cellular Mechanisms of Osteoporosis.International journal of molecular sciences · 2023Review
- A Case of Early-Onset Osteoporosis Due to a Novel WNT1 Variant.AACE endocrinology and diabetesArticle
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
contextMutations in WNT1 can cause rare inherited disorders such as osteogenesis imperfecta (OI) and early-onset osteoporosis (EOOP). Owing to its rarity, the clinical characteristics and pathogenic mechanism of WNT1 mutations remain unclear.
objectiveWe aimed to explore the phenotypic and genotypic spectrum and treatment responses of a large cohort of patients with WNT1-related OI/OP and the molecular mechanisms of WNT1 variants.
methodsThe phenotypes and genotypes of patients and their responses to bisphosphonates or denosumab were evaluated. Western blot analysis, quantitative polymerase chain reaction, and immunofluorescence staining were used to evaluate the expression levels of WNT1, total β-catenin, and type I collagen in the tibial bone or skin from one patient.
resultsWe included 16 patients with 16 mutations identified in WNT1, including a novel mutation. The types of WNT1 mutations were related to skeletal phenotypes, and biallelic nonsense mutations or frameshift mutations could lead to an earlier occurrence of fragility fractures and more severe skeletal phenotypes. Some rare comorbidities were identified in this cohort, including cerebral abnormalities, hematologic diseases, and pituitary adenoma. Bisphosphonates and denosumab significantly increased the spine and proximal hip BMD of patients with WNT1 mutations and reshaped the compressed vertebrae. We report for the first time a decreased β-catenin level in the bone of patient 10 with c.677C > T and c.502G > A compared to the healthy control, which revealed the potential mechanisms of WNT1-induced skeletal phenotypes.
conclusionBiallelic nonsense mutations or frameshift mutations of WNT1 could lead to an earlier occurrence of fragility fractures and a more severe skeletal phenotype in OI and EOOP induced by WNT1 mutations. The reduced osteogenic activity caused by WNT pathway downregulation could be a potential pathogenic mechanism of WNT1-related OI and EOOP.
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