A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone
Authors' conclusion
The observation of recurrent mutations highlights the causative role of PFN1 (L112P) in early-onset PDB/giant cell tumor within the Chinese population and provides insights into the physio-pathological functions of Profilin 1.
Study context
- Population
- A second Chinese family affected by early-onset paget disease of bone (PDB) with malignant giant cell tumors; mouse model carrying the c.335T>C mutation in Pfn1
- Outcome
- Genetic, clinical and mouse-model findings
Methodological detailsfamily genetic study, mouse model
- Family genetic study
- Mouse model
Main finding
As reported in the abstract
- Same heterozygous missense mutation (c.335T>C/p. L112P) in PFN1 identified as in a previously reported family
- PFN1 L112P mutation did not induce ALS in affected individuals
- Early-onset PDB patients had a significantly poorer response to denosumab vs typical PDB patients
- Heterozygous mice showed PDB-like phenotypes (skeletal deformities, focal osteoclastic lesions with giant osteoclasts), no ALS-like phenotypes
- Pfn1 mutation led to enhanced actin ring-like structures at bone surfaces without affecting nuclear factor-κB activation in osteoclast cultures
Original publication
A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone. J Clin Endocrinol Metab. Published 3 June 2025. doi:10.
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