Characterization of FRG2 gene family in the framework of FSHD

This project has been approved for funding - the activation procedure is still pending

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2023

Facioscapulohumeral muscular dystrophy (FSHD) is the third hereditary myopathy worldwide. FSHD is characterized by progressive wasting of specific muscles, and  twenty-percent of patients become wheelchair bound. FSHD has been associated with a peculiar DNA defect: at the end of one chromosome 4 there is a reduced number of copies of DNA segments, named D4Z4, whose reduction in copies (>11 in the healthy population and <8 in FSHD) causes changes in the chromosome structure  bringing nearby genes to be expressed inappropriately. This anomalous activation seems to be crucial for disease onset. However, carriers of  reduced number of D4Z4  do not always develop disease and symptoms in affected people are variable also in the same family. Todate, it is not clear which factors cause these differences.This lack of knowledge hinders the developing of treatments and significantly affects clinical practice. Thus, we aim at  characterizing a family of genes, called FRG2 (FSHD region gene 2) whose functions are unknown. Among these genes, FRG2A, located on chromosome 4, proximal to D4Z4, is expressed at high levels in the muscles of FSHD patients. By studying other genes of the FRG2  family, we discovered that other FRG2s (FRG2B, FRG2C and FRG2-C1) are also variously expressed in cells from FSHD patients and the pattern of this expression varies in each individual. By investigating these genes in affected and healthy carriers from the same family we aim at explaining the clinical differences observed in FSHD families. This approach is essential for the construction of personalized clinical interventions.