Mutations in the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells are considered to be involved in the pathogenesis of PAM.
We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs.
Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations <i>in vivo</i>.
PAM is pathologically attributable to the formation and aggregation of calcium phosphate microliths in the alveoli after mutations in the SLC34A2 gene (the type IIb sodium-phosphate cotransporter gene) coding NaPi-IIb.
Pulmonary alveolar microlithiasis (PAM) is caused by genetic variants in the <i>SLC34A2</i> gene, which encodes the sodium-dependent phosphate transport protein 2B.
PAM has been reported to arise from inactivating mutations in SLC34A2, encoding a sodium-dependent phosphate co-transporter essential for phosphate transport in the lungs and small intestine.