Should the GCM2 gene be tested when screening for familial primary hyperparathyroidism?

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Primary hyperparathyroidism (PHPT) is a condition with sporadic or inherited forms.
• Germline mutations in MEN1, CDC73, and CASR are common causes of PHPT.
• Emerging genes like GCM2 are implicated in PHPT but not routinely screened.

Purpose of the Study:

• To evaluate the significance of GCM2 genetic analysis in PHPT.
• To determine if GCM2 should be incorporated into standard PHPT genetic screening panels.

Main Methods:

• The TENGEN network analyzed allelic variants in GCM2.
• Data from 713 French patients with PHPT undergoing genetic testing were collected.
• Clinical characteristics of GCM2-positive patients were interpreted.

Main Results:

• GCM2 variants were found in 6.6% (85/713) of PHPT patients.
• Twelve variants of uncertain or likely pathogenic significance were identified in 47 patients.
• GCM2 variants can exhibit low penetrance, as observed in a large family study.

Conclusions:

• GCM2 variants identified in the French population are described and interpreted.
• GCM2 gene analysis is recommended for PHPT genetic screening.
• Asymptomatic carriers of GCM2 variants should be monitored for calcemia.