SLC29A3-related syndromes are ultrarare genetic disorders that can cause immune dysfunction, skin abnormalities, and other systemic symptoms. Our study identified new genetic mutations in affected individuals, revealing a possible ancestral link among certain cases. Using advanced computational methods, we examined how these mutations disrupt protein structure and function. We also found that these genetic changes may alter immune system activity and blood cell development. These insights improve our understanding of the disease, aiding earlier diagnosis and targeted treatments. Our findings pave the way for personalized medicine approaches to better care for individuals with SLC29A3-related conditions. (By Dr. Hassan Vahidnezhad, https://jmg.bmj.com/content/early/2025/03/18/jmg-2024-110606 )