Further analysis of PAM patient sequences revealed rare variants in other genes potentially altering the levels of ROS and/or affecting osteoclast differentiation including the transcription factor NFATc1, CSF1R, NOXO, DUOX1, RYR1, RYR2, and RYR3. Interestingly, the NFATc1 gene is a master regulator of RANKL-induced osteoclastogenesis and the Nfatc1 conditional knockout mouse develops osteopetrosis, a condition characterized by increased bone density due to decreased or absent osteoclast activity (Aliprantis et al, 2008). Here, RYR1 is linked to osteopetrosis.