Heterozygous RAD50 gene variant in a family with systemic sclerosis suggests role of impaired DNA repair mechanisms in disease pathogenesis

In the present study, a heterozygous nonsense variant in Exon 21 (c.3229C>T; p.Arg1077*) of the RAD50 gene was identified in a family with multiple systemic sclerosis (SSc) cases, suggesting its significance in the disease's pathogenesis. The RAD50 gene encodes a protein critical for DNA repair and is central in the DNA damage response/repair (DDR/R) network. The RAD50 variant might be the possible cause of diffuse cutaneous SSc in familial cases, implicating genomic instability due to a defective DDR/R network as a potential mechanism.