Myeloid neoplasms risks for germline DDX41 pathogenic variants carriers.

This study investigates the cancer risk associated with germline monoallelic pathogenic variants (PVs) in DDX41, which predispose individuals to myeloid neoplasms (MNs) such as myelodysplastic syndrome and acute myeloid leukemia.

Researchers analyzed 63 families with affected probands and genotyped 160 relatives. They found that carriers of familial DDX41 PVs have a markedly increased lifetime risk of MN, estimated at 19.5% by age 70, with a relative risk 55 times greater than the general population.

Key findings include:

• Increased risk in males: Although the risk appeared higher in males, this was not statistically significant.
• Monitoring recommendations: Annual blood count monitoring is supported, starting at age 50 for DDX41 PV carriers.
• Sex-specific considerations: Earlier cases in females suggest potential need for sex-specific surveillance strategies.