HDR syndrome is primarily caused by mutations in GATA3, encoding a transcription factor whose role is to regulate epigenetic gene expression, located on chromosome 10p (10p14). GATA3 is involved in embryonic development of the parathyroid glands, auditory system, kidneys as well as the thymus and CNS. Identifiable GATA3 mutations are not present in all patients with clinical features compatible with HDR syndrome, with the possibility of the presence of other gene defects associated with this disorder. Observations suggest that successive generations may exhibit earlier onset and greater severity of disease.
GATA3 is primary expressed in breast and urothelial tissue. The protein functions in immune regulation by regulating T-cell development. Missense mutations, nonsense mutations, silent mutations, frameshift insertions and deletions, and in-frame insertions and deletions have been observed in lymphomas, sarcomas and cancers of the skin, head, neck, brain, ovary, biliary tract, breast, lung, intestines, pancreas and bladder. GATA3 has also been shown to play a role in allergic diseases, atopic disease, inflammatory diseases, glomerular disease, Paget disease, Parkinson’s disease, and others.
GATA3