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DC Field | Value | Language |
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dc.contributor.author | Hendricks, Linda A.J. | - |
dc.contributor.author | Hoogerbrugge, Nicoline | - |
dc.contributor.author | Venselaar, Hanka | - |
dc.contributor.author | Aretz, Stefan | - |
dc.contributor.author | Spier, Isabel | - |
dc.contributor.author | Legius, Eric | - |
dc.contributor.author | Brems, Hilde | - |
dc.contributor.author | De Putter, Robin | - |
dc.contributor.author | Claes, Kathleen B.M. | - |
dc.contributor.author | Evans, D. Gareth | - |
dc.contributor.author | Woodward, Emma R. | - |
dc.contributor.author | Genuardi, Maurizio | - |
dc.contributor.author | Brugnoletti, Fulvia | - |
dc.contributor.author | Van Ierland, Yvette | - |
dc.contributor.author | Dijke, Kim | - |
dc.contributor.author | Tham, Emma | - |
dc.contributor.author | Tesi, Bianca | - |
dc.contributor.author | Schuurs Hoeijmakers, Janneke H.M. | - |
dc.contributor.author | Branchaud, Maud | - |
dc.contributor.author | Salvador, Hector | - |
dc.contributor.author | Jahn, Arne | - |
dc.contributor.author | Schnaiter, Simon | - |
dc.contributor.author | Anastasiadou, Violetta Christophidou | - |
dc.contributor.author | Brunet, Joan | - |
dc.contributor.author | Oliveira, Carla | - |
dc.contributor.author | Roht, Laura | - |
dc.contributor.author | Blatnik, Ana | - |
dc.contributor.author | Irmejs, Arvids | - |
dc.contributor.author | Mensenkamp, Arjen R. | - |
dc.contributor.author | Vos, Janet R. | - |
dc.contributor.author | Duijkers, Floor | - |
dc.contributor.author | Giltay, Jacques C. | - |
dc.contributor.author | Van Hest, Liselotte P. | - |
dc.contributor.author | Kleefstra, Tjitske | - |
dc.contributor.author | Leter, Edward M. | - |
dc.contributor.author | Nielsen, Maartje | - |
dc.contributor.author | Nijmeijer, Sebastiaan W.R. | - |
dc.contributor.author | Olderode-berends, Maran J.W. | - |
dc.date.accessioned | 2022-12-23T08:39:51Z | - |
dc.date.available | 2022-12-23T08:39:51Z | - |
dc.date.issued | 2022-12-01 | - |
dc.identifier.issn | 1878-0849 | - |
dc.identifier.uri | http://hdl.handle.net/2445/191809 | - |
dc.description.abstract | Background: Pathogenic PTEN germline variants cause PTEN Hamartoma Tumor Syndrome (PHTS), a rare disease with a variable genotype and phenotype. Knowledge about these spectra and genotype-phenotype associations could help diagnostics and potentially lead to personalized care. Therefore, we assessed the PHTS genotype and phenotype spectrum in a large cohort study. Methods: Information was collected of 510 index patients with pathogenic or likely pathogenic (LP/P) PTEN variants (n = 467) or variants of uncertain significance. Genotype-phenotype associations were assessed using logistic regression analyses adjusted for sex and age.Results: At time of genetic testing, the majority of children (n = 229) had macrocephaly (81%) or developmental delay (DD, 61%), and about half of the adults (n = 238) had cancer (51%), macrocephaly (61%), or cutaneous pathology (49%). Across PTEN, 268 LP/P variants were identified, with exon 5 as hotspot. Missense variants (n = 161) were mainly located in the phosphatase domain (PD, 90%) and truncating variants (n = 306) across all domains. A trend towards 2 times more often truncating variants was observed in adults (OR = 2.3, 95%CI = 1.5-3.4) and patients with cutaneous pathology (OR = 1.6, 95%CI = 1.1-2.5) or benign thyroid pathology (OR = 2.0, 95%CI = 1.1-3.5), with trends up to 2-4 times more variants in PD. Whereas patients with DD (OR = 0.5, 95%CI = 0.3-0.9) or macrocephaly (OR = 0.6, 95%CI = 0.4-0.9) had about 2 times less often truncating variants compared to missense variants. In DD patients these missense variants were often located in domain C2.Conclusion: The PHTS phenotypic diversity may partly be explained by the PTEN variant coding effect and the combination of coding effect and domain. PHTS patients with early-onset disease often had missense variants, and those with later-onset disease often truncating variants. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.ejmg.2022.104632 | - |
dc.relation.ispartof | European Journal of Medical Genetics, 2022, vol. 65, issue. 12, p. 104632 | - |
dc.relation.uri | https://doi.org/10.1016/j.ejmg.2022.104632 | - |
dc.rights | cc by-nc-nd (c) Hendricks, Linda A.J. et al., 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Oncologia | - |
dc.subject.classification | Genètica humana | - |
dc.subject.classification | Fenotip | - |
dc.subject.other | Oncology | - |
dc.subject.other | Human genetics | - |
dc.subject.other | Phenotype | - |
dc.title | Genotype-phenotype associations in a large PTEN Hamartoma Tumor Syndrome (PHTS) patient cohort | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-12-19T12:45:18Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36270489 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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1-s2.0-S1769721222002130-main.pdf | 3.03 MB | Adobe PDF | View/Open |
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