Type I gastric neuroendocrine tumors (gNETs) classically arise because of hypergastrinemia and involve destruction of parietal cells, which are responsible for gastric acid secretion through the ATP4A proton pump and for intrinsic factor production.
By whole exome sequencing, we studied a family with three members with gNETs plus hypothyroidism and rheumatoid arthritis to uncover their genetic origin.
A heterozygous missense mutation in the ATP4A gene was identified. Carriers of this variant had low ferritin and vitamin B
Both mutations suggest that a collaborative mechanism is operative in this family, in which mutations in these genes affect the function and viability of parietal cells and lead to the achlorhydria that drives hypergastrinemia and the formation of gNETs.