“…SLC20A2 is the most common PFBC gene; heterozygous variants have been identified in more than 60% of genetically confirmed PFBC patients [ 3 ]. A missense change is the most common variant type, followed by frameshift, nonsense, and splice site variations, without obvious hotspots for pathogenic variants ( Figure 1 a) [ 3 , 6 , 7 , 17 , 18 , 21 , 23 , 37 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Functionally, both haploinsufficiency and dominant negative effects have been described; the loss of normal PiT2 function results in extracellular Pi accumulation and subsequent calcium phosphate formation [ 6 , 42 ].…”