New gene for Paget's disease discovered

It has long been recognised that genetic factors play an important role in Paget’s disease. Over the past twenty years, advances in human molecular genetics have resulted in the identification of variants in thirteen genes that predispose to the disease. Recently, a group of researchers from the Institute of Genetics and Biophysics in Naples, Italy, added another gene to the list. [2020]

The researchers performed genome sequencing in a large family where several members were affected by Paget’s disease, and identified an abnormality in the PFN1 gene, as the cause of the disease.

Further studies showed that the abnormality in PFN1 caused the gene to malfunction, leading to increased activity of the bone resorbing cells (osteoclasts), which accounted for the occurrence of Paget’s disease. They also found that about 1.8% of individuals with Paget’s disease in this region of Italy were deficient in a copy of this gene.  An interesting aspect of this study is the fact that PFN1 abnormalities had previously been identified in people with certain rare forms of neurological disease and muscle weakness. Therefore, PFN1 joins a growing list of genes where abnormalities can, in some people, cause Paget’s disease but in others cause disease of the nervous system or muscle.  

It is unclear, as yet, whether PFN1 mutations occur in other populations such as the UK, or are relatively specific to the Italian population but this will be investigated in the Genetic Analysis to Predict the Development of Paget’s Disease (GAPDPD) study, which was featured in the August 2020 edition of the Paget's News magazine.

Reference
Scotto di Carlo F, Pazzaglia L, Esposito T, Gianfrancesco F. (2020). The Loss of Profilin 1 Causes Early Onset Paget's Disease of Bone. J Bone Miner Res. 35:1387-1398. doi: 10.1002/jbmr.3964.

This summary was published in Paget's News, the magazine of the Paget's Association, in 2020.