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Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes
Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions’ pathogenic effects at the genetic and epigenetic level...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456353/ https://www.ncbi.nlm.nih.gov/pubmed/36077416 http://dx.doi.org/10.3390/ijms231710017 |
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author | Tritto, Viviana Eoli, Marica Paterra, Rosina Redaelli, Serena Moscatelli, Marco Rusconi, Francesco Riva, Paola |
author_facet | Tritto, Viviana Eoli, Marica Paterra, Rosina Redaelli, Serena Moscatelli, Marco Rusconi, Francesco Riva, Paola |
author_sort | Tritto, Viviana |
collection | PubMed |
description | Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions’ pathogenic effects at the genetic and epigenetic levels are currently unknown. We here report on 22q12 microdeletions’ characterization in three NF2 patients with different phenotype complexities. A possible effect of the position was investigated by in silico analysis of 22q12 topologically associated domains (TADs) and regulatory elements, and by expression analysis of 12 genes flanking patients’ deletions. A 147 Kb microdeletion was identified in the patient with the mildest phenotype, while two large deletions of 561 Kb and 1.8 Mb were found in the other two patients, showing a more severe symptomatology. The last two patients displayed intellectual disability, possibly related to AP1B1 gene deletion. The microdeletions change from one to five TADs, and the 22q12 chromatin regulatory landscape, according to the altered expression levels of four deletion-flanking genes, including PIK3IP1, are likely associated with an early ischemic event occurring in the patient with the largest deletion. Our results suggest that the identification of the deletion extent can provide prognostic markers, predictive of NF2 phenotypes, and potential therapeutic targets, thus overall improving patient management. |
format | Online Article Text |
id | pubmed-9456353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94563532022-09-09 Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes Tritto, Viviana Eoli, Marica Paterra, Rosina Redaelli, Serena Moscatelli, Marco Rusconi, Francesco Riva, Paola Int J Mol Sci Article Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions’ pathogenic effects at the genetic and epigenetic levels are currently unknown. We here report on 22q12 microdeletions’ characterization in three NF2 patients with different phenotype complexities. A possible effect of the position was investigated by in silico analysis of 22q12 topologically associated domains (TADs) and regulatory elements, and by expression analysis of 12 genes flanking patients’ deletions. A 147 Kb microdeletion was identified in the patient with the mildest phenotype, while two large deletions of 561 Kb and 1.8 Mb were found in the other two patients, showing a more severe symptomatology. The last two patients displayed intellectual disability, possibly related to AP1B1 gene deletion. The microdeletions change from one to five TADs, and the 22q12 chromatin regulatory landscape, according to the altered expression levels of four deletion-flanking genes, including PIK3IP1, are likely associated with an early ischemic event occurring in the patient with the largest deletion. Our results suggest that the identification of the deletion extent can provide prognostic markers, predictive of NF2 phenotypes, and potential therapeutic targets, thus overall improving patient management. MDPI 2022-09-02 /pmc/articles/PMC9456353/ /pubmed/36077416 http://dx.doi.org/10.3390/ijms231710017 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tritto, Viviana Eoli, Marica Paterra, Rosina Redaelli, Serena Moscatelli, Marco Rusconi, Francesco Riva, Paola Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title | Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title_full | Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title_fullStr | Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title_full_unstemmed | Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title_short | Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes |
title_sort | characterization of 22q12 microdeletions causing position effect in rare nf2 patients with complex phenotypes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456353/ https://www.ncbi.nlm.nih.gov/pubmed/36077416 http://dx.doi.org/10.3390/ijms231710017 |
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