Genotypic and Phenotypic Spectrum and Pathogenesis of WNT1 Variants in a Large Cohort of Patients With Osteogenesis Imperfecta (OI)/Osteoporosis
Authors' conclusion
Biallelic 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.
Study context
- Population
- Patients with WNT1-related osteogenesis imperfecta (OI) or early-onset osteoporosis (EOOP)
- Participants
- 16 WNT1 mutations
- Outcome
- Genotype–phenotype spectrum
Main finding
As reported in the abstract
Novel WNT1 mutation identified
1
Observational data: associations, not effects.
Further findings
Response to bisphosphonates or denosumab
- Bisphosphonates and denosumab significantly increased spine and proximal hip BMD and reshaped compressed vertebrae
Bone β-catenin (patient 10, c.677C > T and c.502G > A)
- Decreased β-catenin level in bone vs healthy control
Original publication
Genotypic and Phenotypic Spectrum and Pathogenesis of WNT1 Variants in a Large Cohort of Patients With OI/Osteoporosis. J Clin Endocrinol Metab. Published 3 January 2023. doi:10.
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