RRM2B and mitochondrial neurogastrointestinal encephalomyopathy: For example, mutations in RRM2B can cause MNGIE-like symptoms by disrupting the docking interface of the ribonucleoside reductase small subunit homodimer, thereby impairing ribonucleoside reductase activity and damaging the mitochondrial nucleotide pool, which leads to mtDNA depletion.493 Mutations in LIG3, the only mtDNA ligase essential for mtDNA replication and repair, also affect mtDNA maintenance and have been reported in patients with MNGIE, leading to mtDNA depletion.494