Telomere biology disorders gain a family member Comment

In this issue of Blood, Sharma et al report the discovery of novel pathogenic variants in replication protein A1 (RPA1, encoded by RPA1) as a new cause of telomere biology disorders (TBDs).(1) This highly effective multi-institutional collaboration characterized the clinical manifestations in 4 individuals from 4 families, uncovered biology suggesting a role for RPA1 in hematopoiesis, built upon understanding of RPA1's role in telomeric DNA binding and unfolding, and discovered the somatic rescue of the mutation in a patient. This discovery advances understanding of RPA function in telomere biology and, importantly, helps families understand the cause of their illness and their long diagnostic journey and sets the stage for further advances in understanding the role of telomere biology and DNA repair in human disease.

Automated summary

In this study, novel pathogenic variants in RPA1 were discovered as a new cause of TBDs. The researchers investigated the clinical manifestations in patients from different families, and revealed the role of RPA1 in hematopoiesis and telomeric DNA binding and unfolding. The discovery enhances our understanding of RPA function in telomere biology and provides valuable information for families in understanding the cause of their illness.