Comprehensive Analysis of Clinical Features in Index Cases With Multiple Endocrine Neoplasia Type 1 Refine the Risk Rate for Detection of Mutation Distinguishing Negative-Mutation (Phenocopies) and Positive-Mutation Cases
| Autor: | Louise V Antonio, Betsaida Urtremari, Delmar M. Lourenço, Flavio G Ribeiro, Elisangela P S Quedas, Lucas Santos de Santana, Rafael Aquino de Carvalho, Palloma C Lugeiro |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phenocopy
Genetics congenital hereditary and neonatal diseases and abnormalities endocrine system endocrine system diseases business.industry Endocrinology Diabetes and Metabolism Biology medicine.disease Hormone Actions in Tumor Biology: From New Mechanisms to Therapy Text mining Mutation (genetic algorithm) medicine Tumor Biology business Multiple endocrine neoplasia AcademicSubjects/MED00250 |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | Background: Index cases clinically diagnosed with multiple endocrine neoplasia type 1 (MEN1) are declared as MEN1 phenocopies if no germline MEN1 mutation is identified. In comparison with positive-mutation cases, most phenocopies have been diagnosed in older age, mainly by association of primary hyperparathyroidism (HPT) and pituitary adenoma (PIT), with HPT predominantly diagnosed as uniglandular disease. Besides that, phenocopies rarely develop a third MEN1-related tumor and are associated with lower morbidity and longer survival. However, all these data are mainly derived of genetic studies by Sanger targeted to MEN1 gene from a strict number of MEN1 phenocopies. Objectives: to recognize strong clinical profiles capable of predicting the occurrence or absence of germline MEN1 mutation refining the clinical differentiation of phenocopies and mutation-positive cases before genetic testing disclosure. Casuistic/Methods: 143 MEN1 index cases: 87 MEN1-positive and 56 true MEN1 phenocopies (excluded mutations for MLPA assay and by a mini-painel based on long-range PCR and next generation sequencing of 6 MEN1-related genes (MEN1, p15, p18, p21, p27, AIP) covering full coding and non-coding regions. Results: High detectability rate of MEN1 mutation was associated with the presence of ≥ 4 organs affected for primary tumors (100%), association of HPT/PET (neuroendocrine pancreatic tumor)/PIT (93%), HPT/PET (81%), positive familial history (88% vs. 48%), presence of PET (84%) as malign (80%) as multifocal (95%), two different PETs (100%), multiglandular HPT (81%) and diagnosis of one MEN1-related tumor (93%) or of two/three MEN1 tumors diagnosed before 21y (100%). The combination HPT/PIT has the lowest rate of detection of mutation (33%), it is even lower if PIT was acromegaly (12%) or age at the diagnosis of HPT and PIT was, respectively, > 45y and >30y (8%) and absent if it is added uniglandular HPT (0%) or if there was association HPT/PIT (age-independent) with uniglandular HPT (0%). The prediction for detection of mutation increases if these HPT (> 45y)/PIT (> 30y) cases have multiglandular HPT (20%) and it is 100% with association HPT (< 30y)/PIT (< 21y). A p |
| Databáze: | OpenAIRE |
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