Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort

Frontiers in Endocrinology

Endocrinology

Valeria Arsentales¹  Rocío Pareja¹  Isabel Mazarico-Altisent¹  Ismael Capel¹  Andreea Muntean¹  Assumpta Caixàs¹  Mercedes Rigla¹  Neus Baena²  Maria Rosa Bella-Cueto³  Santi Barcons⁴  Xavier Guirao⁴ 

[1] Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d’Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain;Genetic Department, Parc Taulí University Hospital, Institut d’Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain;Pathology Department, Parc Taulí University Hospital, Institut d’Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain;Surgery Department, Parc Taulí University Hospital, Institut d’Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain;

关键词: parathyroid;    primary hyperparathyroidism;    multiple endocrine neoplasia type 1;    multiple endocrine neoplasia type 4;    cyclin-dependent kinase inhibitors;    familial hyperparathyroidism;    familial hypocalciuric hypercalcemia;   

DOI  :  10.3389/fendo.2023.1244361

 received in 2023-06-22, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundApproximately 10% of primary hyperparathyroidism cases are hereditary, due to germline mutations in certain genes. Although clinically relevant, a systematized genetic diagnosis is missing due to a lack of firm evidence regarding individuals to test and which genes to evaluate.MethodsA customized gene panel (AIP, AP2S1, CASR, CDC73, CDKN1A, CDKN1B, CDKN2B, CDKN2C, GCM2, GNA11, MEN1, PTH, RET, and TRPV6) was performed in 40 patients from the Mediterranean area with suspected familial hyperparathyroidism (≤45 years of age, family history, high-risk histology, associated tumour, multiglandular disease, or recurrent hyperparathyroidism). We aimed to determine the prevalence of germline variants in these patients, to clinically characterize the probands and their relatives, and to compare disease severity in carriers versus those with a negative genetic test.ResultsGermline variants were observed in 9/40 patients (22.5%): 2 previously unknown pathogenic/likely pathogenic variants of CDKN1B (related to MEN4), 1 novel variant of uncertain significance of CDKN2C, 4 variants of CASR (3 pathogenic/likely pathogenic variants and 1 variant of uncertain significance), and 2 novel variants of uncertain significance of TRPV6. Familial segregation studies allowed diagnosis and early treatment of PHPT in first-degree relatives of probands.ConclusionThe observed prevalence of germline variants in the Mediterranean cohort under study was remarkable and slightly higher than that seen in other populations. Genetic screening for suspected familial hyperparathyroidism allows the early diagnosis and treatment of PHPT and other related comorbidities. We recommend genetic testing for patients with primary hyperparathyroidism who present with high-risk features.

【 授权许可】

Unknown   
Copyright © 2023 Mazarico-Altisent, Capel, Baena, Bella-Cueto, Barcons, Guirao, Pareja, Muntean, Arsentales, Caixàs and Rigla