HSP60

HRPT2

The HRPT2 gene, also known as CDC73, is a critical component in the regulation of cell growth and division. It encodes a protein that is part of the PAF1 complex, which is involved in transcriptional elongation and histone modification. Mutations in the HRPT2 gene are associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT), a rare genetic condition that predisposes individuals to parathyroid tumors and other neoplasms.

Function

The HRPT2 gene product, parafibromin, is a tumor suppressor protein. It plays a significant role in the regulation of gene expression by associating with the PAF1 complex. This complex is involved in the transcriptional regulation of genes by RNA polymerase II. Parafibromin is crucial for maintaining normal cell cycle progression and preventing uncontrolled cell proliferation.

Clinical Significance

Mutations in the HRPT2 gene can lead to the development of hyperparathyroidism-jaw tumor syndrome. This autosomal dominant disorder is characterized by:

• Primary hyperparathyroidism, often due to parathyroid adenomas or carcinomas.
• Ossifying fibromas of the jaw.
• Renal and uterine tumors.

Patients with HPT-JT have a higher risk of developing parathyroid carcinoma, a rare but aggressive form of cancer. Genetic testing for HRPT2 mutations can be crucial for early diagnosis and management of the syndrome.

Molecular Pathology

HRPT2 mutations are typically inactivating, leading to loss of function of the parafibromin protein. This loss of function disrupts the normal regulatory mechanisms of the cell cycle, contributing to tumorigenesis. The most common types of mutations include nonsense mutations, frameshift mutations, and splice site mutations.

Diagnosis and Management

Diagnosis of HPT-JT involves genetic testing for HRPT2 mutations, along with clinical evaluation for symptoms of hyperparathyroidism and jaw tumors. Management strategies include:

• Surgical removal of parathyroid tumors.
• Regular monitoring for the development of other associated tumors.
• Genetic counseling for affected families.

Research Directions

Ongoing research is focused on understanding the precise molecular mechanisms by which HRPT2 mutations lead to tumorigenesis. There is also interest in developing targeted therapies that can compensate for the loss of parafibromin function.

Also see

• Hyperparathyroidism
• Parathyroid carcinoma
• Tumor suppressor gene
• Genetic testing