Should all patients with hyperparathyroidism be screened for a CDC73 mutation?

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Primary hyperparathyroidism (PH) is a common endocrine disorder, occasionally linked to genetic syndromes like hyperparathyroidism-jaw tumour syndrome (HPT-JT) and familial isolated hyperparathyroidism (FIHP).
• Inactivating mutations in the CDC73 tumor suppressor gene are a known cause of HPT-JT and FIHP, but whole gene deletions are exceptionally rare.

Purpose of the Study:

• To report a rare case of PH caused by a large chromosomal deletion encompassing the entire CDC73 gene.
• To emphasize the importance of genetic screening for young PH patients and the need for molecular testing methods capable of detecting large deletions.

Main Methods:

• Case report of a 39-year-old woman with PH due to a parathyroid adenoma.
• Detection of a 2.5 Mb chromosomal deletion encompassing the entire CDC73 gene using molecular testing.
• Review of the patient's medical history, including parathyroidectomy.

Main Results:

• A large chromosomal deletion (2.5 Mb) involving the complete CDC73 gene was identified in a patient with PH.
• This deletion was detected years after the patient's initial parathyroidectomy, highlighting diagnostic delays.

Conclusions:

• Young patients with hyperparathyroidism require genetic screening to identify underlying genetic etiologies, including rare CDC73 deletions.
• Molecular diagnostic techniques must be capable of detecting large deletions, not just point mutations, for comprehensive genetic assessment.
• Surveillance for patients with CDC73 mutations should include monitoring calcium and parathyroid hormone levels, dental assessments, and screening for uterine and renal tumors.