A team led by researchers at St. Anna Children's Cancer Research Institute in Vienna has identified rare, X-linked germline mutations in DOCK11 in a handful of patients with otherwise unexplained immune system and hematological symptoms. As they report in the New England Journal of Medicine, the researchers sequenced four male patients with similar presentations to uncover four hemizygous variants in the DOCK11 gene. DOCK11 is expressed largely in hematopoietic cells and, though it has a role in B cell development in mice, its role in people is mostly unknown. In a series of assays, the St. Anna's team found that while the DOCK11 gene variants they found affect B cell development, they also affect T cell development and lead to T cell overactivation, which can lead to organ damage. "The protein appears to play a role in keeping the activation of T cells within a certain range," first author Jana Block, a PhD student at St. Anna's and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, says in a statement. Block and colleagues add that stem cell transplants or gene therapy could treat the disease, though more research is needed.
Rare, X-Linked Variants in DOCK11 Implicated in Handful of Patients
Jun 22, 2023