The risk of developing PC is approximately 15% in patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder characterized by the germline mutation in the hypoxanthine phosphoribosyltransferase 2 (HRPT2), which encodes protein parafibromin.
HRPT2 mutations have been identified in sporadic PC, but not in adenoma or hyperplasia.
Genetic counseling found a mutation in CDC73 (HRPT2).
A linkage between hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is linked to a chromosomal mutation in HRPT2, and renal diseases was published in a previous study, where two families with HPT-JT syndrome were followed and found to have adult renal hamartomas and cystic kidney disease as prominent features; and this possibly represented a new phenotypic variant of the HPTJT syndrome.
Primary hyperparathyroidism and jaw tumor syndrome: A novel mutation of the HRPT2
Similar to MEN-1, HPT-JT is a rare autosomal dominant disorder that arises from mutations in the CDC73 (HRPT2
) tumor suppressor gene.
Parafibromin is a protein coded by the CDC73/ HRPT2
gene and consists of 531 amino acids.
(6) Pimenta et al, reported association of a new tumor suppressor gene (HRPT2
) mutation with ossifying fibroma and proposed that these tumors could develop as a result of haplo in sufficiency of the particular gene.
The [beta]-catenin/LEF/TCF complexes have been shown to interact with a variety of other nuclear factors to control specific transcriptional targets which include c-Myc, p300, CBP, Hrpt2
, Foxo, Bcl9-2, reptin, pontin, c-Jun, Grouchos, Prmt2, CtBP, and cyclin D1 [239-241].
A rare genetic syndrome, hereditary hyperparathyroidism with jaw tumor syndrome, is correlated with mutations in the HRPT2
There is an association with the HRPT2
gene (1q25-q31), which is associated with hyperparathyroidism-jaw tumor syndrome (an autosomal dominant disorder).
gene (for "hyperparathyroidism 2") is a putative tumor suppressor gene that was identified and has been mapped to 1q25-q31.