GCM2 Variants in Familial and Multiglandular Primary Hyperparathyroidism.

Autor:	Vincze S; Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT, USA., Peters NV; Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA., Kuo CL; Biostatistics Center, Connecticut Institute for Clinical and Translational Science, University of Connecticut, Farmington, CT, USA., Brown TC; Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.; Department of Surgery, Washington University School of Medicine, St. Louis, MO,USA., Korah R; Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA., Murtha TD; Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA., Bellizzi J; Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT, USA., Riccardi A; Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT, USA.; Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Parham K; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, USA., Carling T; Biostatistics Center, Connecticut Institute for Clinical and Translational Science, University of Connecticut, Farmington, CT, USA.; Carling Adrenal Center, Hospital for Endocrine Surgery, Tampa, FL, USA., Costa-Guda J; Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT, USA.; Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine, Farmington, CT, USA., Arnold A; Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT, USA.; Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, CT, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 Apr 19; Vol. 107 (5), pp. e2021-e2026.
DOI:	10.1210/clinem/dgab929
Abstrakt:	Context: Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of parathyroid development, were observed in familial isolated hyperparathyroidism and sporadic PHPT. However, as these previously reported GCM2 variants occur at relatively high frequencies in the population, understanding their potential clinical utility will require both additional penetrance data and functional evidence relevant to tumorigenicity. Objective: Determine the frequency of GCM2 variants of interest among patients with sporadic multigland or familial parathyroid disease and assess their penetrance. Design and Patients: DNA-encoding PHPT-associated GCM2 germline variants were polymerase chain reaction-amplified and sequenced from 107 patients with either sporadic multigland or suspected/confirmed familial parathyroid tumors. Results: GCM2 variants were observed in 9 of 107 cases (8.4%): Y282D in 4 patients (6.3%) with sporadic multigland disease; Y394S in 2 patients (11.1%) with familial PHPT and 3 (4.8%) with sporadic multigland disease. Compared with the general population, Y282D was enriched 5.9-fold in multigland disease, but its penetrance was very low (0.02%). Y394S was enriched 79-fold in sporadic multigland disease and 93-fold in familial PHPT, but its penetrance was low (1.33% and 1.04%, respectively). Conclusions: Observed in vitro-activating GCM2 variant alleles are significantly overrepresented in PHPT patients with multiglandular or familial disease compared to the general population, yet penetrance values are very low; that is, most individuals with these variants in the population have a very low risk of developing PHPT. The potential clinical utility of detecting these GCM2 variants requires further investigation, including assessing their possible role as pathogenic/low-penetrance alleles. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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