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Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism
PURPOSE: CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 m...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023768/ https://www.ncbi.nlm.nih.gov/pubmed/36334246 http://dx.doi.org/10.1007/s40618-022-01948-7 |
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author | Mazarico-Altisent, I. Capel, I. Baena, N. Bella-Cueto, M. R. Barcons, S. Guirao, X. Albert, L. Cano, A. Pareja, R. Caixàs, A. Rigla, M. |
author_facet | Mazarico-Altisent, I. Capel, I. Baena, N. Bella-Cueto, M. R. Barcons, S. Guirao, X. Albert, L. Cano, A. Pareja, R. Caixàs, A. Rigla, M. |
author_sort | Mazarico-Altisent, I. |
collection | PubMed |
description | PURPOSE: CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). METHODS: During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. RESULTS: DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. CONCLUSION: Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-022-01948-7. |
format | Online Article Text |
id | pubmed-10023768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-100237682023-03-19 Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism Mazarico-Altisent, I. Capel, I. Baena, N. Bella-Cueto, M. R. Barcons, S. Guirao, X. Albert, L. Cano, A. Pareja, R. Caixàs, A. Rigla, M. J Endocrinol Invest Original Article PURPOSE: CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). METHODS: During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. RESULTS: DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. CONCLUSION: Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-022-01948-7. Springer International Publishing 2022-11-05 2023 /pmc/articles/PMC10023768/ /pubmed/36334246 http://dx.doi.org/10.1007/s40618-022-01948-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Mazarico-Altisent, I. Capel, I. Baena, N. Bella-Cueto, M. R. Barcons, S. Guirao, X. Albert, L. Cano, A. Pareja, R. Caixàs, A. Rigla, M. Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title_full | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title_fullStr | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title_full_unstemmed | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title_short | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism |
title_sort | novel germline variants of cdkn1b and cdkn2c identified during screening for familial primary hyperparathyroidism |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023768/ https://www.ncbi.nlm.nih.gov/pubmed/36334246 http://dx.doi.org/10.1007/s40618-022-01948-7 |
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